プロフィール詳細

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Jill J.に依頼

United Kingdom

Experienced proofreader in biological and medical sciences

プロフィール概要

Dr Jill Johnson is a Lecturer and Principal Investigator at Aston University in Birmingham, UK. Dr Johnson’s current research interests focus on the role of pericytes in chronic lung disease, specifically investigating the progenitor cell capacity of these cells and their ability to contribute to the pathogenesis of pulmonary fibrosis

専門分野

• ★ Biology/Life Sciences
• ☆ Stem Cell Research
• ☆ Medicine
• ☆ Pulmonology/Respiratory Disease

サービス

• Writing
• Research
• Consulting
• Data & AI
• Product Development

Writing Clinical Trial Documentation, Technical Writing, Copywriting, Newswriting

Research Market Research, Meta-Research, Feasibility Study, Gap Analysis

Consulting Scientific and Technical Consulting

Data & AI Statistical Analysis, Big Data Analytics

Product Development Formulation

職務経験

Aston University

- 現在

Lecturer

Aston University

6月 2016 - 現在

Research Fellow

Imperial College London

12月 2011 - 4月 2016

Postdoctoral Fellow

McGill University

2月 2011 - 11月 2011

Postdoctoral Fellow

Karolinska Institutet

1月 2008 - 12月 2010

学歴

PhD (Health Science)

McMaster University

9月 2002 - 8月 2007

B.Sc. (Science)

McMaster University

9月 1997 - 4月 2002

認定資格

• 認定資格の詳細は未入力です。

出版物

JOURNAL ARTICLE

Macrophages: the Good, the Bad, and the Gluttony @article{8b8ac97b1e1545b7b1f78e4630640f43, title = "Macrophages: the Good, the Bad, and the Gluttony", abstract = "Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile and interpret recent findings on the plasticity of macrophages and how these cells contribute to the development of non-infectious inflammatory diseases, with a particular focus on allergic and autoimmune disorders. The critical roles of macrophages in the resolution of inflammation will then be examined, emphasizing the ability of macrophages to clear apoptotic immune cells. Rheumatoid arthritis (RA) is a chronic autoimmune-driven spectrum of diseases where persistent inflammation results in synovial hyperplasia and excessive immune cell accumulation, leading to remodeling and reduced function in affected joints. Macrophages are central to the pathophysiology of RA, driving episodic cycles of chronic inflammation and tissue destruction. RA patients have increased numbers of active M1 polarized pro-inflammatory macrophages and few or inactive M2 type cells. This imbalance in macrophage homeostasis is a main contributor to pro-inflammatory mediators in RA, resulting in continual activation of immune and stromal populations and accelerated tissue remodeling. Modulation of macrophage phenotype and function remains a key therapeutic goal for the treatment of this disease. Intriguingly, therapeutic intervention with glucocorticoids or other DMARDs promotes the re-polarization of M1 macrophages to an anti-inflammatory M2 phenotype; this reprogramming is dependent on metabolic changes to promote phenotypic switching. Allergic asthma is associated with Th2-polarised airway inflammation, structural remodeling of the large airways, and airway hyperresponsiveness. Macrophage polarization has a profound impact on asthma pathogenesis, as the response to allergen exposure is regulated by an intricate interplay between local immune factors including cytokines, chemokines and danger signals from neighboring cells. In the Th2-polarized environment characteristic of allergic asthma, high levels of IL-4 produced by locally infiltrating innate lymphoid cells and helper T cells promote the acquisition of an alternatively activated M2a phenotype in macrophages, with myriad effects on the local immune response and airway structure. Targeting regulators of macrophage plasticity is currently being pursued in the treatment of allergic asthma and other allergic diseases. Macrophages promote the re-balancing of pro-inflammatory responses towards pro-resolution responses and are thus central to the success of an inflammatory response. It has long been established that apoptosis supports monocyte and macrophage recruitment to sites of inflammation, facilitating subsequent corpse clearance. This drives resolution responses and mediates a phenotypic switch in the polarity of macrophages. However, the role of apoptotic cell-derived extracellular vesicles (ACdEV) in the recruitment and control of macrophage phenotype has received remarkably little attention. ACdEV are powerful mediators of intercellular communication, carrying a wealth of lipid and protein mediators that may modulate macrophage phenotype, including a cargo of active immune-modulating enzymes. The impact of such interactions may result in repair or disease in different contexts. In this review, we will discuss the origin, characterization, and activity of macrophages in sterile inflammatory diseases and the underlying mechanisms of macrophage polarization via ACdEV and apoptotic cell clearance, in order to provide new insights into therapeutic strategies that could exploit the capabilities of these agile and responsive cells.", author = "Ewan Ross and Andrew Devitt and Jill Johnson", note = "{\textcopyright} 2021 Ross, Devitt and Johnson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Funding: The authors gratefully acknowledge financial support from the UK Biotechnology and Biological Sciences Research Council (BB/S00324X/1).", year = "2021", month = aug, day = "12", doi = "10.3389/fimmu.2021.708186", language = "English", volume = "12", journal = "Frontiers in Immunology", issn = "1664-3224", publisher = "Frontiers Media S.A.", } . Frontiers in Immunology.

Implementing Best Practice in Training Problem-Based Learning Tutors @article{3df07092d70645cf9ac969164651d990, title = "Implementing Best Practice in Training Problem-Based Learning Tutors", abstract = "PurposeIn order to implement problem-based learning (PBL), extensive staff training is required. The purpose of this study was to qualitatively evaluate the efficacy of a training programme for inexperienced PBL tutors.MethodsData included anonymous feedback from programme participants, semi-structured interviews with programme participants, and feedback from students.ResultsData from these independent sources were analysed, resulting in three main themes that painted a comprehensive picture of the success and limitations of the PBL tutor training programme: I) pedagogical knowledge of PBL was obtained but needs to be reinforced by practice; II) the mock tutorial was a relevant experience; III) a written PBL tutor guide supports training efforts.ConclusionsUsing diverse sets of data, this study demonstrated that the acquisition of pedagogical knowledge is contextual and partial, and multiple sources of knowledge are required to achieve a complete and interpretable picture of the subject.", author = "Jill Johnson", note = "This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.", year = "2021", month = apr, day = "28", doi = "10.24313/jpbl.2021.00017", language = "English", volume = "8", pages = "24--34", journal = "Journal of Problem-Based Learning", number = "1", } . Journal of Problem-Based Learning.

Rebecca Bignold, Jill R. Johnson(2021). Effects of cytokine signaling inhibition on inflammation-driven tissue remodeling . Current Research in Pharmacology and Drug Discovery. 2. Microsoft.AspNetCore.Mvc.Localization.LocalizedHtmlString 100023. Elsevier {BV}

Jill R. Johnson, James A. Harker (2017). Allergic Airway Disease: More than Meets the IgE? . American Journal of Respiratory Cell and Molecular Biology.

An official American thoracic society research statement @article{a880db58042d407c846ace42f7f42c8c, title = "An official American thoracic society research statement: Current challenges facing research and therapeutic advances in airway remodeling", abstract = "Background: Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and regulatory issues that deter progress of AR research and development of therapeutics targeting AR and to propose approaches and solutions to these specific problems. This Statement is not intended to provide clinical practice recommendations on any disease in which AR is observed and/or plays a role. Methods: An international multidisciplinary group from within academia, industry, and the National Institutes of Health, with expertise in multimodal approaches to the study of airway structure and function, pulmonary research and clinical practice in obstructive lung disease, and drug discovery platforms was invited to participate in one internet-based and one face-to-face meeting to address the above-stated goals. Although the majority of the analysis related to AR was in asthma, AR in other diseases was also discussed and considered in the recommendations. A literature search of PubMed was performed to support conclusions. The search was not a systematic review of the evidence. Results: Multiple conceptual, logistical, economic, and regulatory deterrents were identified that limit the performance of AR research and impede accelerated, intensive development of AR-focused therapeutics. Complementary solutions that leverage expertise of academia and industry were proposed to address them. Conclusions: To date, numerous factors related to the intrinsic difficulty in performing AR research, and economic forces that are disincentives for the pursuit of AR treatments, have thwarted the ability to understandARpathology and mechanisms and to address it clinically. This ATS Research Statement identifies potential solutions for each of these factors and emphasizes the importance of educating the global research community as to the extent of the problem as a critical first step in developing effective strategies for: (1) increasing the extent and impact of AR research and (2) developing, testing, and ultimately improving drugs targeting AR.", author = "{ATS Assembly on Respiratory Structure and Function} and Prakash, {Y. S.} and Halayko, {Andrew J.} and Reinoud Gosens and Panettieri, {Reynold A.} and Blanca Camoretti-Mercado and Penn, {Raymond B.} and Ram Aiyar and Alaina Ammit and Neville Berkman and Richard Bond and Robert Brown and Louis Boulet and Janette Burgess and Chung, {Kian Fan} and Jason Debley and Deepak Deshpande and Michelle Freemer and Mitchell Glass and Angela Haczku and Stephen Holgate and Charles Irvin and David Jacoby and Jill Johnson and Hermann Meurs and Thomas Murphy and Mahadev Murthy and Patricia Noel and Paul O'Byrne and Christina Pabelick and Tonio Pera and Matthew Poynter and Gary Robinson and Sejal Saglani and Julian Solway and Alastair Stewart and Omar Tliba and Alkis Togias and Prescott Woodruff", year = "2017", month = jan, day = "15", doi = "10.1164/rccm.201611-2248ST", language = "English", volume = "195", pages = "e4--e19", journal = "American Journal of Respiratory and Critical Care Medicine", issn = "1073-449X", publisher = "American Thoracic Society", number = "2", } . American Journal of Respiratory and Critical Care Medicine.

Pericytes, mesenchymal stem cells and their contributions to tissue repair @article{4a94250807184c4fae48dd08d7b9f5dd, title = "Pericytes, mesenchymal stem cells and their contributions to tissue repair", abstract = "Regenerative medicine using mesenchymal stem cells for the purposes of tissue repair has garnered considerable public attention due to the potential of returning tissues and organs to a normal, healthy state after injury or damage has occurred. To achieve this, progenitor cells such as pericytes and bone marrow-derived mesenchymal stem cells can be delivered exogenously, mobilised and recruited from within the body or transplanted in the form organs and tissues grown in the laboratory from stem cells. In this review, we summarise the recent evidence supporting the use of endogenously mobilised stem cell populations to enhance tissue repair along with the use of mesenchymal stem cells and pericytes in the development of engineered tissues. Finally, we conclude with an overview of currently available therapeutic options to manipulate endogenous stem cells to promote tissue repair.", keywords = "Fibrosis, Mesenchymal stem cell, Pericyte, Regenerative medicine, Tissue engineering, Tissue repair", author = "Wong, {Suet Ping} and Rowley, {Jessica E.} and Redpath, {Andia N.} and Tilman, {Jessica D.} and Fellous, {Tariq G.} and Johnson, {Jill R.}", note = "Funding Information: The authors are grateful for the financial support from the UK Medical Research Council (new investigator research grant # MR/K011375/1 ) and the Wellcome Trust (senior investigator award # 095700 ).", year = "2015", month = jul, doi = "10.1016/j.pharmthera.2015.03.006", language = "English", volume = "151", pages = "107--120", journal = "Pharmacology and Therapeutics", issn = "0163-7258", publisher = "Elsevier", } . Pharmacology and Therapeutics.

Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma @article{b103736e16f3497ab9f3024fb893ce01, title = "Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma", abstract = "Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.", keywords = "Airway Remodeling, Airway Resistance, Animals, Asthma, Benzimidazoles, Bronchi, Chronic Disease, Disease Models, Animal, Elasticity, Female, Mice, Inbred C57BL, Muscle, Smooth, Pericytes, Proto-Oncogene Proteins c-sis, Quinolines, Receptor, Platelet-Derived Growth Factor beta, Journal Article, Research Support, Non-U.S. Gov't", author = "Johnson, {Jill R.} and Erika Folestad and Rowley, {Jessica E.} and Noll, {Elisa M.} and Walker, {Simone A.} and Lloyd, {Clare M.} and Rankin, {Sara M.} and Kristian Pietras and Ulf Eriksson and Jonas Fuxe", note = "Copyright {\textcopyright} 2015 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0: {\textcopyright} the American Physiological Society.", year = "2015", month = apr, day = "1", doi = "10.1152/ajplung.00286.2014", language = "English", volume = "308", pages = "L658--L671", journal = "AJP: Lung Cellular and Molecular Physiology", issn = "1040-0605", publisher = "American Physiological Society", number = "7", } . AJP: Lung Cellular and Molecular Physiology.

Jill R. Johnson, Erika Folestad, Jessica E. Rowley, Elisa M. Noll, Simone A. Walker, Clare M. Lloyd, Sara M. Rankin, Kristian Pietras, Ulf Eriksson, Jonas Fuxe(2015). Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma . American Journal of Physiology-Lung Cellular and Molecular Physiology. 308. (7). Microsoft.AspNetCore.Mvc.Localization.LocalizedHtmlString L658--L671. American Physiological Society

(2014). Novel drug targets for asthma and COPD: Lessons learned from in vitro and in vivo models . Pulmonary Pharmacology & Therapeutics.

Novel drug targets for asthma and COPD @article{01c25d4b84b8450eb72dc7efda71449c, title = "Novel drug targets for asthma and COPD: Lessons learned from invitro and invivo models", abstract = "Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyperresponsiveness. Whilst current therapies, such as β-agonists and glucocorticoids, may be effective at reducing symptoms, they do not reduce disease progression. Thus, there is a need to identify new therapeutic targets. In this review, we summarize the potential of novel targets or tools, including anti-inflammatories, phosphodiesterase inhibitors, kinase inhibitors, transient receptor potential channels, vitamin D and protease inhibitors, for the treatment of asthma and COPD.", keywords = "G-protein coupled receptor, Inflammation, Kinase, Therapeutic targets, Transient receptor potential channel, Vitamin D", author = "Baker, {Katie E.} and Bonvini, {Sara J.} and Chantal Donovan and Foong, {Rachel E.} and Bing Han and Aruni Jha and Yasin Shaifta and Marieke Smit and Johnson, {Jill R.} and Moir, {Lyn M.}", year = "2014", month = dec, doi = "10.1016/j.pupt.2014.05.008", language = "English", volume = "29", pages = "181--198", journal = "Pulmonary Pharmacology and Therapeutics", issn = "1094-5539", publisher = "Elsevier", number = "2", } . Pulmonary Pharmacology and Therapeutics.

Pericytes in chronic lung disease @article{7b47a94bee3d4089b9ab5f7a9059f7fa, title = "Pericytes in chronic lung disease", abstract = "Pericytes are mesenchymal cells embedded within the abluminal surface of the endothelium of microvessels such as capillaries, pre-capillary arterioles, post-capillary and collecting venules, where they maintain microvascular homeostasis and participate in angiogenesis. In addition to their roles in supporting the vasculature and facilitating leukocyte extravasation, pericytes have been recently investigated as a subpopulation of mesenchymal stem cells (MSCs) due to their capacity to differentiate into numerous cell types including the classic MSC triad, i.e. osteocytes, chondrocytes and adipocytes. Other studies in models of fibrotic inflammatory disease of the lung have demonstrated a vital role of pericytes in myofibroblast activation, collagen deposition and microvascular remodelling, which are hallmark features of chronic lung diseases such as asthma, chronic obstructive pulmonary disorder, pulmonary fibrosis and pulmonary hypertension. Further studies into the mechanisms of the pericyte- to-myofibroblast transition and migration to fibrotic foci will hopefully clarify the role of these cells in chronic lung disease and confirm the importance of pericytes in human fibrotic pulmonary disease.", keywords = "Allergic asthma, Chronic obstructive pulmonary disorder, Fibrosis, Inflammation, Lung, Stem cells", author = "Rowley, {Jessica E.} and Johnson, {Jill R.}", year = "2014", month = nov, day = "7", doi = "10.1159/000365051", language = "English", volume = "164", pages = "178--188", journal = "International Archives of Allergy and Immunology", issn = "1018-2438", publisher = "S. Karger AG", number = "3", } . International Archives of Allergy and Immunology.

Jessica E. Rowley, Jill R. Johnson(2014). Pericytes in Chronic Lung Disease . International Archives of Allergy and Immunology. 164. (3). Microsoft.AspNetCore.Mvc.Localization.LocalizedHtmlString 178--188. S. Karger {AG}

IL-22 contributes to TGF-β1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells @article{004bb8ad2ccf47a59239dbf2302d2ea7, title = "IL-22 contributes to TGF-β1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells", abstract = "Background: Allergic asthma is characterized by airway inflammation in response to antigen exposure, leading to airway remodeling and lung dysfunction. Epithelial-mesenchymal transition (EMT) may play a role in airway remodeling through the acquisition of a mesenchymal phenotype in airway epithelial cells. TGF-β1 is known to promote EMT; however, other cytokines expressed in severe asthma with extensive remodeling, such as IL-22, may also contribute to this process. In this study, we evaluated the contribution of IL-22 to EMT in primary bronchial epithelial cells from healthy and asthmatic subjects.Methods: Primary bronchial epithelial cells were isolated from healthy subjects, mild asthmatics and severe asthmatics (n=5 patients per group). The mRNA and protein expression of epithelial and mesenchymal cell markers and EMT-associated transcription factors was evaluated following stimulation with TGF-β1, IL-22 and TGF-β1+IL-22.Results: Primary bronchial epithelial cells stimulated with TGF-β1 underwent EMT, demonstrated by decreased expression of epithelial markers (E-cadherin and MUC5AC) and increased expression of mesenchymal markers (N-cadherin and vimentin) and EMT-associated transcription factors. IL-22 alone had no effect on epithelial or mesenchymal gene expression. However, IL-22+TGF-β1 promoted the expression of some EMT transcription factors (Snail1 and Zeb1) and led to a more profound cadherin shift, but only in cells obtained from severe asthmatics.Conclusion: The impact of IL-22 on airway epithelial cells depends on the cytokine milieu and the clinical phenotype of the patient. Further studies are required to determine the molecular mechanism of IL-22 and TGF-β1 cooperativity in driving EMT in primary human bronchial epithelial cells.", author = "Johnson, {Jill R.} and Michiyoshi Nishioka and Jamila Chakir and Risse, {Paul Andr{\'e}} and Ibrahim Almaghlouth and Bazarbashi, {Ahmad N.} and Sophie Plante and Martin, {James G.} and David Eidelman and Qutayba Hamid", note = "{\textcopyright} 2013 Johnson et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.", year = "2013", month = nov, day = "1", doi = "10.1186/1465-9921-14-118", language = "English", volume = "14", journal = "Respiratory Research", issn = "1465-9921", publisher = "BioMed Central", number = "1", } . Respiratory Research.

Effect of topical corticosteroids on allergic airway inflammation and disease severity in obstructive sleep apnoea @article{753d34e40dd346d286d70636122e3965, title = "Effect of topical corticosteroids on allergic airway inflammation and disease severity in obstructive sleep apnoea", abstract = "Summary: Background: The incidence of sleep-related breathing disorders is correlated with lower and upper airway inflammatory diseases, such as asthma and allergic rhinitis. We hypothesized that corticosteroids treatment would lead to a greater reduction in disease severity in obstructive sleep apnoea syndrome (OSAS) patients with concomitant allergic rhinitis vs. non-allergic OSAS patients by reducing the level of inflammation in upper airway tissues. Objective: This study was performed to determine whether treatment with intranasal corticosteroids could reduce upper airway inflammation and improve sleep parameters in obstructive sleep apnoea syndrome patients with or without concomitant allergic rhinitis. Methods: Obstructive sleep apnoea syndrome patients with (n = 34) or without (n = 21) documented allergic rhinitis voluntarily enrolled in the study and were assessed at baseline and after corticosteroids treatment for 10-12 weeks. Sleep studies were performed and biopsies were obtained from the inferior turbinate, nasopharynx, and uvula. The apnoea-hypopnoea index, sleep quality, and level of daytime alertness were determined, and immunocytochemistry was used to phenotype tissue inflammation. Results: Standard sleep indices improved following treatment in the entire cohort of obstructive sleep apnoea syndrome patients, with greater improvement seen in the allergic rhinitis group. Allergic rhinitis patients demonstrated significantly improved O2 saturation and a lower supine apnoea-hypopnoea index score after corticosteroid treatment; similar improvements were not seen in the non-allergic rhinitis group. Eosinophilia was detected at all three sites in the allergic rhinitis group, but not in the non-allergic rhinitis group. Following treatment, fewer eosinophils and CD4 lymphocytes were documented at all three biopsy sites in the allergic group; the reduction in inflammation was less apparent in the non-allergic rhinitis group.", keywords = "Allergic rhinitis, Corticosteroid, Inflammation, Sleep apnoea", author = "F. Lavigne and Petrof, {B. J.} and Johnson, {J. R.} and P. Lavigne and N. Binothman and Kassissia, {G. O.} and {Al Samri}, M. and C. Giordano and N. Dub{\'e} and D. Hercz and A. Benedetti and Q. Hamid", year = "2013", month = oct, doi = "10.1111/cea.12158", language = "English", volume = "43", pages = "1124--1133", journal = "Clinical and Experimental Allergy", issn = "0954-7894", publisher = "Wiley-Blackwell", number = "10", } . Clinical and Experimental Allergy.

Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination @article{92deecfb55374f678ab78cd67b14afcc, title = "Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination", abstract = "Therapy-induced resistance remains a significant hurdle to achieve long-lasting responses and cures in cancer patients. We investigated the long-term consequences of genetically impaired angiogenesis by engineering multiple tumor models deprived of endoglin, a co-receptor for TGF-β in endothelial cells actively engaged in angiogenesis. Tumors from endoglin-deficient mice adapted to the weakened angiogenic response, and refractoriness to diminished endoglin signaling was accompanied by increased metastatic capability. Mechanistic studies in multiple mouse models of cancer revealed that deficiency for endoglin resulted in a tumor vasculature that displayed hallmarks of endothelial-to-mesenchymal transition, a process of previously unknown significance in cancer biology, but shown by us to be associated with a reduced capacity of the vasculature to avert tumor cell intra- and extravasation. Nevertheless, tumors deprived of endoglin exhibited a delayed onset of resistance to anti-VEGF (vascular endothelial growth factor) agents, illustrating the therapeutic utility of combinatorial targeting of multiple angiogenic pathways for the treatment of cancer.", author = "Charlotte Anderberg and Cunha, {Sara I.} and Zhenhua Zhai and Eliane Cortez and Evangelia Pardali and Johnson, {Jill R.} and Marcela Franco and Marta P{\'a}ez-Ribes and Ross Cordiner and Jonas Fuxe and Johansson, {Bengt R.} and Goumans, {Marie Jos{\'e}} and Oriol Casanovas and Dijke, {Peter ten} and Arthur, {Helen M.} and Kristian Pietras", note = "{\textcopyright} 2013 Anderberg et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).", year = "2013", month = feb, day = "11", doi = "10.1084/jem.20120662", language = "English", volume = "210", pages = "563--579", journal = "Journal of Experimental Medicine ", issn = "0022-1007", publisher = "Rockefeller University Press", number = "3", } . Journal of Experimental Medicine.

Functional phenotype of airway myocytes from asthmatic airways @article{7a32fa67d393436c999d92f41333a35a, title = "Functional phenotype of airway myocytes from asthmatic airways", abstract = "In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a '. healthy' ASM cell become '. asthmatic' still remains speculative. What is known of an '. asthmatic' ASM cell, is its ability to contribute to the hallmarks of asthma such as bronchoconstriction (contractile phenotype), inflammation (synthetic phenotype) and ASM hyperplasia (proliferative phenotype).The phenotype of healthy or diseased ASM cells or tissue for the most part is determined by expression of key phenotypic markers. ASM is commonly accepted to have different phenotypes: the contractile (differentiated) state versus the synthetic (dedifferentiated) state (with the capacity to synthesize mediators, proliferate and migrate). There is now accumulating evidence that the synthetic functions of ASM in culture derived from asthmatic and non-asthmatic donors differ. Some of these differences include an altered profile and increased production of extracellular matrix proteins, pro-inflammatory mediators and adhesion receptors, collectively suggesting that ASM cells from asthmatic subjects have the capacity to alter their environment, actively participate in repair processes and functionally respond to changes in their microenvironment.", keywords = "Airway smooth muscle, Animal models, Asthma, Extracellular matrix, Vascular smooth muscle", author = "Wright, {David B.} and Thomas Trian and Sana Siddiqui and Pascoe, {Chris D.} and Ojo, {Oluwaseun O.} and Johnson, {Jill R.} and Dekkers, {Bart G.J.} and Shyamala Dakshinamurti and Rushita Bagchi and Burgess, {Janette K.} and Varsha Kanabar", year = "2013", month = feb, doi = "10.1016/j.pupt.2012.08.003", language = "English", volume = "26", pages = "95--104", journal = "Pulmonary Pharmacology and Therapeutics", issn = "1094-5539", publisher = "Elsevier", number = "1", } . Pulmonary Pharmacology and Therapeutics.

Smooth muscle in tissue remodeling and hyper-reactivity @article{8bef1df5bbeb4a2887019d2a089b4f6f, title = "Smooth muscle in tissue remodeling and hyper-reactivity: Airways and arteries", abstract = "Smooth muscle comprises a key functional component of both the airways and their supporting vasculature. Dysfunction of smooth muscle contributes to and exacerbates a host of breathing-associated pathologies such as asthma, chronic obstructive pulmonary disease and pulmonary hypertension. These diseases may be marked by airway and/or vascular smooth muscle hypertrophy, proliferation and hyper-reactivity, and related conditions such as fibrosis and extracellular matrix remodeling. This review will focus on the contribution of airway or vascular smooth dysfunction to common airway diseases.", keywords = "Airway smooth muscle, Animal models, Asthma, Chronic obstructive pulmonary disease, Pulmonary hypertension, Vascular smooth muscle", author = "Kristina Rydell-T{\"o}rm{\"a}nen and Risse, {Paul Andr{\'e}} and Varsha Kanabar and Rushita Bagchi and Czubryt, {Michael P.} and Johnson, {Jill R.}", year = "2013", month = feb, doi = "10.1016/j.pupt.2012.04.003", language = "English", volume = "26", pages = "13--23", journal = "Pulmonary Pharmacology and Therapeutics", issn = "1094-5539", publisher = "Elsevier", number = "1", } . Pulmonary Pharmacology and Therapeutics.

Phenotype modulation of airway smooth muscle in asthma @article{f1d7c43c49e845668a1ffb404cce55e3, title = "Phenotype modulation of airway smooth muscle in asthma", abstract = "The biological responses of airway smooth muscle (ASM) are diverse, in part due to ASM phenotype plasticity. ASM phenotype plasticity refers to the ability of ASM cells to change the degree of a variety of functions, including contractility, proliferation, migration and secretion of inflammatory mediators. This plasticity occurs due to intrinsic or acquired abnormalities in ASM cells, and these abnormalities or predisposition of the ASM cell may alter the ASM response and in some cases recapitulate disease hallmarks of asthma.These phenotypic changes are ultimately determined by multiple stimuli and occur due to alterations in the intricate balance or reversible state that maintains ASM cells in either a contractile or synthetic state, through processes termed maturation or modulation, respectively. To elucidate the role of ASM phenotype in disease states, numerous in vitro studies have suggested a phenotypic switch in ASM primary cell cultures as an explanation for the plethora of responses mediated by ASM cells. Moreover, there is overwhelming evidence suggesting that the immunomodulatory response of ASM is due to the acquisition of a synthetic phenotype; however, whether this degree of plasticity is present in vivo as opposed to cell culture-based models remains speculative. Nonetheless, this review will give an overall scope of ASM phenotypic markers, triggers of ASM phenotype modulation and novel therapeutic approaches to control ASM phenotype plasticity.", keywords = "Airway smooth muscle, Asthma, Contractile response, Phenotypic plasticity, Synthetic response", author = "Wright, {David B.} and Thomas Trian and Sana Siddiqui and Pascoe, {Chris D.} and Johnson, {Jill R.} and Dekkers, {Bart G.J.} and Shyamala Dakshinamurti and Rushita Bagchi and Burgess, {Janette K.} and Varsha Kanabar and Ojo, {Oluwaseun O.}", year = "2013", month = feb, doi = "10.1016/j.pupt.2012.08.005", language = "English", volume = "26", pages = "42--49", journal = "Pulmonary Pharmacology and Therapeutics", issn = "1094-5539", publisher = "Elsevier", number = "1", } . Pulmonary Pharmacology and Therapeutics.

Appraising the small airways in asthma @article{75ec4dfc0b154748ba4fbf115f66f808, title = "Appraising the small airways in asthma", abstract = "Purpose of Review: The small airways play an important yet poorly targeted role in asthma pathophysiology, leading to increased morbidity in asthma patients. Assessing inflammation and remodeling in these airways, determining the contribution of small airways to lung dysfunction and enhancing drug delivery to the distal regions of the lung remain challenging. The purpose of this review is to highlight recent advances in our understanding of small airways involvement in asthma. Recent Findings: Inflammation in the small airways can be evaluated through exhaled gas measurements, most often nitric oxide. However, additional exhaled biomarkers have recently been described. Considerable infiltration of mast cells in the distal lung and extensive structural changes to the small airways have also been demonstrated. Advances have been made in the functional assessment of small airways, particularly in the measurement of small airway compliance and ventilation defects and in studies investigating the impact of small particle inhaled corticosteroid treatment on lung function. Summary: Experimental assessments of small airways inflammation, remodeling and function have provided novel insights into the importance of the distal regions of the lung in asthma pathology. Further advances in drug delivery to the small airways have the potential to improve asthma control.", keywords = "asthma, inflammation, pharmacotherapy, physiology, small airways", author = "Johnson, {Jill R.} and Qutayba Hamid", year = "2012", month = jan, doi = "10.1097/MCP.0b013e32834dd8c2", language = "English", volume = "18", pages = "23--28", journal = "Current Opinion in Pulmonary Medicine", issn = "1070-5287", publisher = "Lippincott Williams and Wilkins Ltd.", number = "1", } . Current Opinion in Pulmonary Medicine.

Remodeling in asthma @article{2c85d74be0914060ae367cc8b5105638, title = "Remodeling in asthma", abstract = "Airway remodeling encompasses the structural alterations in asthmatic compared with normal airways. Airway remodeling in asthmatic patients involves a wide array of pathophysiologic features, including epithelial changes, increased smooth muscle mass, increased numbers of activated fibroblasts/myofibroblasts, subepithelial fibrosis, and vascular changes. Multiple cytokines, chemokines, and growth factors released from both inflammatory and structural cells in the airway tissue create a complex signaling environment that drives these structural changes. However, recent investigations have changed our understanding of asthma from a purely inflammatory disease to a disease in which both inflammatory and structural components are equally involved. Several reports have suggested that asthma primarily develops because of serious defects in the epithelial layer that allow environmental allergens, microorganisms, and toxins greater access to the airway tissue and that can also stimulate the release of mediators from the epithelium, thus contributing to tissue remodeling. Lung-resident fibroblasts and smooth muscle cells have also been implicated in the pathogenesis of airway remodeling. Remodeling is assumed to result in persistent airflow limitation, a decrease in lung function, and airway hyperresponsiveness. Asthmatic subjects experience an accelerated decrease in lung function compared with healthy subjects, which is proportionally related to the duration and severity of their disease.", keywords = "airway smooth muscle, Asthma, corticosteroid, fibrosis, remodeling", author = "Saleh Al-Muhsen and Johnson, {Jill R.} and Qutayba Hamid", year = "2011", month = sep, doi = "10.1016/j.jaci.2011.04.047", language = "English", volume = "128", pages = "451--462", journal = "Journal of Allergy and Clinical Immunology", issn = "0091-6749", publisher = "Mosby Inc.", number = "3", } . Journal of Allergy and Clinical Immunology.

Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways @article{ffa6217b6e0641c78d33365236c8ea98, title = "Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways", abstract = "Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM) extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1) levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA) and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.", author = "Johnson, {Jill R.} and Abraham Roos and Tove Berg and Magnus Nord and Jonas Fuxe", note = "{\textcopyright} 2011 Johnson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.", year = "2011", month = jan, day = "20", doi = "10.1371/journal.pone.0016175", language = "English", volume = "6", journal = "PLoS ONE", issn = "1932-6203", publisher = "Public Library of Science", number = "1", } . PLoS ONE.

A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-β mediated epithelial-mesenchymal transition @article{76445a5d82c54e0ea0d901e629538af5, title = "A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-β mediated epithelial-mesenchymal transition", abstract = "Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-β (TGF-β) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT. The SNAIL1-SMAD3/4 complex was targeted to the gene promoters of CAR, a tight-junction protein, and E-cadherin during TGF-β-driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells. Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited repression of CAR and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma and at the invasive fronts of human breast cancer. We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene repression during EMT.", author = "Theresa Vincent and Neve, {Etienne P.A.} and Johnson, {Jill R.} and Alexander Kukalev and Federico Rojo and Joan Albanell and Kristian Pietras and Ismo Virtanen and Lennart Philipson and Leopold, {Philip L.} and Crystal, {Ronald G.} and {de Herreros}, {Antonio Garcia} and Aristidis Moustakas and Pettersson, {Ralf F.} and Jonas Fuxe", year = "2009", month = jul, day = "13", doi = "10.1038/ncb1905", language = "English", volume = "11", pages = "943--950", journal = "Nature Cell Biology", issn = "1465-7392", publisher = "Nature Publishing Group", number = "8", } . Nature Cell Biology.

Evaluation of allergic lung inflammation by computed tomography in a rat model in vivo @article{6f49927f700e489e83aa01738334bc81, title = "Evaluation of allergic lung inflammation by computed tomography in a rat model in vivo", abstract = "The ability of micro-computed tomography (CT) to noninvasively evaluate allergic pulmonary inflammation in an experimental model was investigated. In addition, two image segmentation methods and the value of respiratory gating were investigated in the context of this model. Brown Norway rats were exposed to one of four doses of house dust mite (HDM) extract (0, 0.15, 15 or 150 μg) delivered intratracheally every 24 h for 10 days. CT scanning was performed at baseline and after several longitudinal HDM exposures. Both thoracic- and lung-segmentation methods yielded similar results when standardisation practices were employed. While tissue histology correlated well with CT images, cell counts from bronchoalveolar lavage depicted greater inflammation than did density measures from CT images. Evidence from representative CT slices and transaxial density distribution indicated that inflammation was primarily associated with major airways and extended into the periphery from these focal points. Respiratory gating demonstrated that images of the inspiratory state provided greater contrast of inflammatory processes. Lastly, decreases in tidal volumes indicated significant mechanical respiratory changes in animals exposed to both 15 and 150 μg. In summary, CT image segmentation can extract pertinent data on in vivo allergic airway/lung inflammation. Furthermore, respiratory gating provides additional contrast and insight into these quantification practices. Copyright", keywords = "Allergy, Animal model, Asthma, Computed tomography, Noninvasive assessment", author = "Jobse, {B. N.} and Johnson, {J. R.} and Farncombe, {T. H.} and R. Labiris and Walker, {T. D.} and S. Goncharova and M. Jordana", year = "2009", month = jun, doi = "10.1183/09031936.00087508", language = "English", volume = "33", pages = "1437--1447", journal = "European Respiratory Journal", issn = "0903-1936", publisher = "Wiley", number = "6", } . European Respiratory Journal.

Combined budesonide/formoterol therapy in conjunction with allergen avoidance ameliorates house dust mite-induced airway remodeling and dysfunction @article{c02b221ac2ad451cb61f611a378d69b6, title = "Combined budesonide/formoterol therapy in conjunction with allergen avoidance ameliorates house dust mite-induced airway remodeling and dysfunction", abstract = "Allergic asthma is characterized by airway inflammation in response to chronic allergen exposure, resulting in remodeling of the airway wall accompanied by dysfunctional airway physiology. However, a link between the immune-inflammatory response to allergen and changes to airway structure and physiology has not yet been fully elucidated. Moreover, the impact of inhaled corticosteroids and β2-agonists, the primary pharmacotherapy for asthma, on this process has not been completely evaluated. In this study, we employed a murine model of chronic exposure to a common environmental aeroallergen, house dust mite, to recapitulate the phenotype of clinical asthma. By examining the therapeutic effects of corticosteroid/β2- agonist combination therapy with budesonide/formoterol (BUD/FORM) in this model of airway disease, we endeavored to determine the impact of BUD/FORM on lung inflammation, structure, and physiology. BUD/FORM was delivered either while allergen exposure was ongoing (concurrent therapy) or following the cessation of allergen exposure (postexposure therapy). Our results show that airway inflammation was substantially reduced in BUD/FORM-treated mice in the concurrent therapy group, whereas in the postexposure therapy group airway inflammation spontaneously resolved. In contrast, BUD/FORM was most effective in resolving several aspects of airway remodeling and bronchial hyperreactivity when delivered in conjunction with allergen withdrawal. This study demonstrates that although both BUD/FORM therapy and allergen avoidance independently reduce airway inflammation, only BUD/FORM therapy in conjunction with allergen avoidance can effectively reverse airway remodeling and bronchial hyperreactivity induced by chronic allergen exposure.", keywords = "Airway hyperreactivity, Asthma, Pharmacotherapy", author = "Johnson, {Jill R.} and Pacitto, {Stephanie R.} and Jonathan Wong and Archer, {Elliot W.} and Stefan Eirefelt and Anna Miller-Larsson and Manel Jordana", year = "2008", month = nov, doi = "10.1152/ajplung.90229.2008", language = "English", volume = "295", pages = "L780--L788", journal = "AJP: Lung Cellular and Molecular Physiology", issn = "1040-0605", publisher = "American Physiological Society", number = "5", } . American Journal of Physiology - Lung Cellular and Molecular Physiology.

Induction of vascular remodeling in the lung by chronic house dust mite exposure @article{86d69487266a4f26ae4ed86e06e2c353, title = "Induction of vascular remodeling in the lung by chronic house dust mite exposure", abstract = "Structural changes to the lung are associated with chronic asthma. In addition to alterations to the airway wall, asthma is associated with vascular modifications, although this aspect of remodeling is poorly understood. We sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. Because many ovalbumin-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we used a protocol of chronic respiratory exposure to house dust mite extract (HDME), which has been shown to induce persistent airway inflammation consistent with that seen in humans with asthma. Mice were exposed to HDME intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks after the end of a 7-week exposure protocol. Measures of vascular remodeling, including total collagen deposition, procollagen I production, endothelial and smooth muscle cell proliferation, smooth muscle area, and presence of myofibroblasts, were investigated histologically in lung vessels of different sizes and locations. We observed an increase in total collagen content, which did not resolve upon cessation of allergen exposure. Other parameters were significantly increased after 7 and/or 20 weeks of allergen exposure but returned to baseline after allergen withdrawal. We conclude that respiratory HDME exposure induces airway remodeling and pulmonary vascular remodeling, and, in accordance with airway remodeling, some components of these structural changes may be irreversible.", keywords = "House dust mite, Myofibroblast, Procollagen I, Smooth muscle, Vascular remodeling", author = "Kristina Rydell-T{\"o}rm{\"a}nen and Johnson, {Jill R.} and Ramzi Fattouh and Manel Jordana and Erjef{\"a}lt, {Jonas S.}", year = "2008", month = jul, day = "1", doi = "10.1165/rcmb.2007-0441OC", language = "English", volume = "39", pages = "61--67", journal = "American Journal of Respiratory Cell and Molecular Biology", issn = "1044-1549", publisher = "American Thoracic Society", number = "1", } . American Journal of Respiratory Cell and Molecular Biology.

Transforming growth factor-β regulates house dust mite-induced allergic airway inflammation but not airway remodeling @article{a2a65049169242d49e1b459ff4905e6c, title = "Transforming growth factor-β regulates house dust mite-induced allergic airway inflammation but not airway remodeling", abstract = "Rationale: It is now believed that both chronic airway inflammation and remodeling contribute significantly to airway dysfunction and clinical symptoms in allergic asthma. Transforming growth factor (TGF)-β is a powerful regulator of both the tissue repair and inflammatory responses, and numerous experimental and clinical studies suggest that it may play an integral role in the pathogenesis of asthma. Objectives: We investigated the role of TGF-β in the regulation of allergic airway inflammation and remodeling using a mouse model of house dust mite (HDM)-induced chronic allergic airway disease. Methods: We have previously shown that intranasal administration of an HDM extract (5 d/wk for 5 wk) elicits robust Th2-polarized airway inflammation and remodeling that is associated with increased airway hyperreactivity. Here, Balb/c mice were similarly exposed to HDM and concurrently treated with a pan-specific TGF-β neutralizing antibody. Measurements and Main Results: We observed that anti-TGF-β treatment in the context of either continuous or intermittent HDM exposure had no effect on the development of HDM-induced airway remodeling. To further confirm these findings, we also subjected SMAD3 knockout mice to 5 weeks of HDM and observed that knockout mice developed airway remodeling to the same extent as HDM-exposed littermate controls. Notably, TGF-β neutralization exacerbated the eosinophilic infiltrate and led to increased airway hyperreactivity. Conclusions: Collectively, these data suggest that TGF-β regulates HDM-induced chronic airway inflammation but not remodeling, and furthermore, caution against the use of therapeutic strategies aimed at interfering with TGF-β activity in the treatment of this disease.", keywords = "Allergic asthma, Immunology, Lung, Mouse model", author = "Ramzi Fattouh and Midence, {N. Gabriela} and Katherine Arias and Johnson, {Jill R.} and Walker, {Tina D.} and Susanna Goncharova and Souza, {Kailene P.} and Gregory, {Richard C.} and Scott Lonning and Jack Gauldie and Manel Jordana", year = "2008", month = mar, day = "15", doi = "10.1164/rccm.200706-958OC", language = "English", volume = "177", pages = "593--603", journal = "American Journal of Respiratory and Critical Care Medicine", issn = "1073-449X", publisher = "American Thoracic Society", number = "6", } . American Journal of Respiratory and Critical Care Medicine.

Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes @article{29b210473a2447d69a3a1abd8e8ca4aa, title = "Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes", abstract = "Asthma is a chronic airway inflammatory disease that encompasses three cardinal processes: T helper (Th) cell type 2 (Th2)-polarized inflammation, bronchial hyperreactivity, and airway wall remodeling. However, the link between the immune-inflammatory phenotype and the structural-functional phenotype remains to be fully defined. The objective of these studies was to evaluate the relationship between the immunologic nature of chronic airway inflammation and the development of abnormal airway structure and function in a mouse model of chronic asthma. Using IL-4-competent and IL-4-deficient mice, we created divergent immune-inflammatory responses to chronic aeroallergen challenge. Immune-inflammatory, structural, and physiological parameters of chronic allergic airway disease were evaluated in both strains of mice. Although both strains developed airway inflammation, the profiles of the immune-inflammatory responses were markedly different: IL-4-competent mice elicited a Th2-polarized response and IL-4-deficient mice developed a Th1-polarized response. Importantly, this chronic Th1-polarized immune response was not associated with airway remodeling or bronchial hyperresponsiveness. Transient reconstitution of IL-4 in IL-4-deficient mice via an airway gene transfer approach led to partial Th2 repolarization and increased bronchial hyperresponsiveness, along with full reconstitution of airway remodeling. These data show that distinct structural-functional phenotypes associated with chronic airway inflammation are strictly dependent on the nature of the immune-inflammatory response.", keywords = "Allergy, Inflammation, Lung, Th1/Th2 cells", author = "Johnson, {Jill R.} and Swirski, {Filip K.} and Gajewska, {Beata U.} and Wiley, {Ryan E.} and Ramzi Fattouh and Pacitto, {Stephanie R.} and Wong, {Jonathan K.} and St{\"a}mpfli, {Martin R.} and Manel Jordana", year = "2007", month = sep, doi = "10.1152/ajplung.00056.2007", language = "English", volume = "293", pages = "L730--L739", journal = "AJP: Lung Cellular and Molecular Physiology", issn = "1040-0605", publisher = "American Physiological Society", number = "3", } . American Journal of Physiology - Lung Cellular and Molecular Physiology.

House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation @article{d50d87cce7b14793a03b6169e01bf40f, title = "House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation", abstract = "Rationale: Mouse models of allergic airway disease have greatly contributed to our understanding of disease induction and pathogenesis. Although these models typically investigate responses to a single antigen or allergen, humans are frequently exposed to a myriad of allergens, each with distinct antigenic potential. Objectives: Given that airway exposure to ovalbumin (OVA), a prototypic innocuous antigen, induces inhalation tolerance, we wished to investigate how this response would be altered if OVA were encountered concurrently with a house dust mite extract (HDM), which we have recently shown is capable of eliciting a robust allergic airway inflammatory response that is mediated, at least in part, by granulocyte-macrophage colony-stimulating factor. Methods: Balb/c mice were exposed daily to HDM (intranasally) followed immediately by exposure to aerosolized OVA for 5 weeks. To allow the inflammatory response elicited by HDM to subside fully, mice were then allowed to rest, unexposed, for 8 weeks, at which time they were rechallenged with aerosolized OVA for 3 consecutive days. Measurements and Main Results: At this time, we observed a robust eosinophilic inflammatory response in the lung that was associated with an increase in bronchial hyperreactivity. Moreover, we documented significantly elevated serum levels of OVA-specific IgE and IgG 1 and increased production of the Th2 cytokines interleukin 4 (1L-4), 1L-5, and IL-13 by splenocytes stimulated in vitro with OVA. Conclusion: Our data demonstrate the potential of a potent allergen such as HDM to establish a lung microenvironment that fosters the development of allergic sensitization to otherwise weak or innocuous antigens, such as OVA.", keywords = "Allergic sensitization, Allergy inflammation, Lung, Mouse", author = "Ramzi Fattouh and Pouladi, {Mahmoud A.} and David Alvarez and Johnson, {Jill R.} and Walker, {Tina D.} and Susanna Goncharova and Inman, {Mark D.} and Manel Jordana", year = "2005", month = aug, day = "1", doi = "10.1164/rccm.200502-198OC", language = "English", volume = "172", pages = "314--321", journal = "American Journal of Respiratory and Critical Care Medicine", issn = "1073-449X", publisher = "American Thoracic Society", number = "3", } . American Journal of Respiratory and Critical Care Medicine.

B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance @article{cd99828db2844556a148d48c1dd8d700, title = "B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance", abstract = "The recently described ICOS-B7RP-1 costimulatory pathway has been implicated in the generation of effector Th2 responses and, hence, has become an attractive therapeutic target for allergic diseases. In the present study, we used B7KP-1-deficient mice to investigate the role of B7RP-1 in the generation and maintenance of Th2 responses in a model of mucosal allergic airway inflammation. We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context of GM-CSF leads to airway eosinophilic inflammation. This response was long lasting because rechalleage of mice with the same Ag recapitulated airway eosinophilia. Moreover, significant expression of T1/ST2 on T cells and production of Th2-affiliated cytokines (IL-5, IL-4, and IL-13) and Igs (IgE and IgG1) conclusively demonstrate the generation of a Th2 response in the absence of B7RP-1. In audition, expression of two major Th2-associated costimulatory molecules-CD28 and ICOS-indicates T cell activation in the absence of B7RP-1 signaling. Finally, B7RP-1 knockout mice are resistant to the induction of inhalation tolerance as indicated by the sustained eostaophilia in the lung and IL-5 production. In summary, our results demonstrate that in a model of mucosal allergic sensitization, the ICOS-B7RP-1 pathway is redundant for the generation of Th2 responses but essential for the induction of inhalation tolerance.", author = "Gajewska, {Beata U.} and Anna Tafuri and {\'S}wirski, {Filip K.} and Tina Walker and Johnson, {Jill R.} and Theresa Shea and Arda Shahinian and Susanna Goncharova and Mak, {Tak W.} and St{\"a}mpfli, {Martin R.} and Manel Jordana", year = "2005", month = mar, day = "1", doi = "10.4049/jimmunol.174.5.3000", language = "English", volume = "174", pages = "3000--3005", journal = "Journal of Immunology", issn = "0022-1767", publisher = "American Association of Immunologists", number = "5", } . Journal of Immunology.

Concomitant airway expression of granulocyte-macrophage colony-stimulating factor and decorin, a natural inhibitor of transforming growth factor-β, breaks established inhalation tolerance @article{a667660e21a24dbb8ce009e312f839fe, title = "Concomitant airway expression of granulocyte-macrophage colony-stimulating factor and decorin, a natural inhibitor of transforming growth factor-β, breaks established inhalation tolerance", abstract = "We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) breaks tolerance induction. The objective of this study was to determine whether GM-CSF breaks established inhalation tolerance. To induce tolerance, BALB/c mice were exposed to aerosolized ovalbumin (OVA) for 10 consecutive days. A control group was exposed to saline. Subsequently, tolerant and control animals were exposed to OVA in a GM-CSF-enriched airway microenvironment. Tolerant animals, unlike control animals, did not develop airway and peripheral blood eosinophilia, had diminished levels of OVA-specific IgE, and reduced airway hyper-responsiveness. While tolerant animals did not express IL-4, IL-5 and IL-13, levels of the regulatory cytokines IL-10, IFN-γ and transfoming growth factor (TGF)-β were similar between tolerant and non-tolerant animals. Lung CD4+ T cells were activated according to CD69, CD25 and T1/ST2 expression, but systemic responses characterized by splenocyte proliferation and Th2 effector function were dramatically reduced. Concurrent expression of GM-CSF and decorin, a natural inhibitor of TGF-β, reversed eosinophilic unresponsiveness. Our study suggests that the breakdown of tolerance and, by extension, the emergence of eosinophilic inflammation, requires two signals: one that triggers sensitization and one that interferes with negative regulation. Moreover, our study shows that dysregulated expression of an extracellular matrix protein may break established tolerance and lead to eosinophilic airway inflammation.", keywords = "Allergy, GM-CSF, Lung, TGF-β, Tolerance", author = "Swirski, {Filip K.} and Gajewska, {Beata U.} and Robbins, {Clinton S.} and Abigail D'Sa and Johnson, {Jill R.} and Pouladi, {Mahmoud A.} and Inman, {Mark D.} and St{\"a}mpfli, {Martin R.}", note = "Funding: This study was supported in part by the Canadian Institutes of Health Research, the Hamilton Health Sciences Corporation, and St. Joseph's Hospital. F.K.S. is holder of a K. M. Hunter/Canadian Institutes for Health Research (CIHR) Doctoral Research Award. C.S.R. and J.R.J. are holders of an Ontario Graduate Scholarship (OGS).", year = "2004", month = sep, doi = "10.1002/eji.200425012", language = "English", volume = "34", pages = "2375--2386", journal = "European Journal of Immunology", issn = "0014-2980", publisher = "Wiley", number = "9", } . European Journal of Immunology.

Transient Corticosteroid Treatment Permanently Amplifies the Th2 Response in a Murine Model of Asthma @article{d0ed848e295e433693697c5485c5d1cf, title = "Transient Corticosteroid Treatment Permanently Amplifies the Th2 Response in a Murine Model of Asthma", abstract = "Corticosteroids (CS) remain the most efficacious pharmacotherapeutic option for the management of asthma. Although the acute anti-inflammatory effects of CS treatment have been amply documented both clinically and experimentally, recent human data intimate that exposure to CS may be associated with retrograde immune phenomena, including enhanced synthesis of IgE in vivo and elevated Th2 cytokine production in vitro. We have investigated the long-term immunologic effects of CS treatment in a murine model of allergic airway inflammation. CS treatment during initial exposure to OVA or upon long-term Ag rechallenge remarkably attenuated eosinophilic airway inflammation and airway hyperresponsiveness. Interestingly, however, Th2 cytokine production by cultured splenocytes from CS-treated mice was significantly elevated, while IFN-γ synthesis was depressed. Moreover, mice rechallenged with OVA several weeks after CS intervention during allergic sensitization not only developed airway inflammation, but also exhibited enhanced Th2 cytokine production in lymphoid tissues and OVA-specific IgE in serum. This amplification of the systemic immune response was associated with an intact APC compartment during CS-conditioned sensitization to OVA. These data indicate that immune processes underlying the allergic phenotype remain impervious to CS treatment and raise the possibility that treatment with CS during sensitization may amplify elements of the allergen-specific immune response.", author = "Wiley, {Ryan E.} and Monika Cwiartka and David Alvarez and Mackenzie, {David C.} and Johnson, {Jill R.} and Susanna Goncharova and Lennart Lundblad and Manel Jordana", year = "2004", month = apr, day = "15", doi = "10.4049/jimmunol.172.8.4995", language = "English", volume = "172", pages = "4995--5005", journal = "Journal of Immunology", issn = "0022-1767", publisher = "American Association of Immunologists", number = "8", } . Journal of Immunology.

Continuous Exposure to House Dust Mite Elicits Chronic Airway Inflammation and Structural Remodeling @article{bf56af02c2964e72b30fbb6ceb4d750d, title = "Continuous Exposure to House Dust Mite Elicits Chronic Airway Inflammation and Structural Remodeling", abstract = "It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly.", keywords = "Allergy and immunology, Animal, Asthma, Models", author = "Johnson, {Jill R.} and Wiley, {Ryan E.} and Ramzi Fattouh and Swirski, {Filip K.} and Gajewska, {Beata U.} and Coyle, {Anthony J.} and Gutierrez-Ramos, {Jos{\'e} Carlos} and Russ Ellis and Inman, {Mark D.} and Manel Jordana", year = "2004", month = feb, day = "1", doi = "10.1164/rccm.200308-1094oc", language = "English", volume = "169", pages = "378--385", journal = "American Journal of Respiratory and Critical Care Medicine", issn = "1073-449X", publisher = "American Thoracic Society", number = "3", } . American Journal of Respiratory and Critical Care Medicine.

Evaluation of inducible costimulator/B7-related protein-1 as a therapeutic target in a murine model of allergic airway inflammation @article{d8c5203b878049468bce2b6055877c4d, title = "Evaluation of inducible costimulator/B7-related protein-1 as a therapeutic target in a murine model of allergic airway inflammation", abstract = "Given its primary role in the execution of T cell, and especially Th2, effector activity, the inducible costimulator (ICOS)/B7-related protein (RP)-1 costimulatory pathway is currently being heralded as a promising therapeutic target for immune-inflammatory disorders such as asthma. This study investigates the merits of ICOS blockade in a murine model of experimental asthma in which mice are sensitized to ovalbumin (OVA) through the respiratory mucosa. Intraperitoneal treatment of mice with anti-ICOS neutralizing antibody during sensitization resulted in a marked reduction in airway eosinophilia and IL-5 in bronchoalveolar lavage, but had no effect on interleukin (IL)-4, IL-13, and eotaxin content in bronchoalveolar lavage or the production of OVA-specific immunoglobulin E in serum. Cultured splenocytes from mice sensitized to OVA in the context of ICOS ablation produced enhanced levels of IL-4 and IL-5 upon stimulation with OVA, and this correlated with elevated inflammation and immunoglobulin E secretion upon long-term in vivo OVA recall; the deleterious effects ICOS blockade, however, were not associated with reduced IL-10 production by splenocytes. Peculiarly, anti-ICOS intervention during OVA rechallenge had no effect on airway inflammation or immunoglobulin production, despite high levels of ICOS expression on infiltrating CD4+ T cells. This study provides in vivo evidence of an exacerbated long-term immune-inflammatory response following acute ICOS blockade, and suggests that ICOS costimulation is functionally redundant in established allergic disease.", author = "Wiley, {Ryan E.} and Susanna Goncharova and Theresa Shea and Johnson, {Jill R.} and Coyle, {Anthony J.} and Manel Jordana", year = "2003", month = jun, day = "1", doi = "10.1165/rcmb.2002-0220OC", language = "English", volume = "28", pages = "722--730", journal = "American Journal of Respiratory Cell and Molecular Biology", issn = "1044-1549", publisher = "American Thoracic Society", number = "6", } . American Journal of Respiratory Cell and Molecular Biology.

Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.

Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination.

Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes.

Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways.

Effect of topical corticosteroids on allergic airway inflammation and disease severity in obstructive sleep apnoea.

Combined budesonide/formoterol therapy in conjunction with allergen avoidance ameliorates house dust mite-induced airway remodeling and dysfunction.

B7RP-1 is not required for the generation of Th2 responses in a model of allergic airway inflammation but is essential for the induction of inhalation tolerance.

A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.

House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation.

IL-22 contributes to TGF-β1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells.

Induction of vascular remodeling in the lung by chronic house dust mite exposure.

Evaluation of allergic lung inflammation by computed tomography in a rat model in vivo.

Evaluation of inducible costimulator/B7-related protein-1 as a therapeutic target in a murine model of allergic airway inflammation.

Transient corticosteroid treatment permanently amplifies the Th2 response in a murine model of asthma.

Transforming growth factor-beta regulates house dust mite-induced allergic airway inflammation but not airway remodeling.

OTHER

Periostin Expression Is Elevated in HDM-Driven Allergic Airway Disease and Associated with Increased Pericyte Migration @article{7e32d03b016648e2adf5f8e4f8198ea5, title = "Periostin Expression Is Elevated in HDM-Driven Allergic Airway Disease and Associated with Increased Pericyte Migration", author = "J. Johnson and R. Bignold", year = "2021", month = may, day = "3", doi = "10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a4495", language = "English", journal = "American Journal of Respiratory and Critical Care Medicine", issn = "1073-449X", publisher = "American Thoracic Society", note = "American Thoracic Society International Conference 2021 ; Conference date: 14-05-2021 Through 19-05-2021", } . American Journal of Respiratory and Critical Care Medicine.

Inflammation-Induced Pericyte Dysfunction Is Abrogated by Interfering with the CXCL12/CXCR4 Signaling Pathway @article{b86be57f536a4fa9a49ecd480d77affb, title = "Inflammation-Induced Pericyte Dysfunction Is Abrogated by Interfering with the CXCL12/CXCR4 Signaling Pathway", author = "J. Johnson and B. Shammout", year = "2021", month = may, day = "3", doi = "10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a4490", language = "English", journal = "American Journal of Respiratory and Critical Care Medicine", issn = "1073-449X", publisher = "American Thoracic Society", note = "American Thoracic Society International Conference 2021 ; Conference date: 14-05-2021 Through 19-05-2021", } . American Journal of Respiratory and Critical Care Medicine.

Allergic airway disease @article{8f93398e4f634b34aa7d7b3555d1dc84, title = "Allergic airway disease: more than meets the IgE?", author = "Johnson, {Jill R.} and Harker, {James A.}", year = "2017", month = dec, day = "31", doi = "10.1165/rcmb.2017-0271ED", language = "English", volume = "57", pages = "631--632", journal = "American Journal of Respiratory Cell and Molecular Biology", issn = "1044-1549", publisher = "American Thoracic Society", number = "6", } . American Journal of Respiratory Cell and Molecular Biology.

BOOK CHAPTER

Pericytes in Chronic Lung Disease @inbook{f4b6041c4bf04641a0d5a1dc031db8f9, title = "Pericytes in Chronic Lung Disease", abstract = "Pericytes are supportive mesenchymal cells located on the abluminal surface of the microvasculature, with key roles in regulating microvascular homeostasis, leukocyte extravasation, and angiogenesis. A subpopulation of pericytes with progenitor cell function has recently been identified, with evidence demonstrating the capacity of tissue-resident pericytes to differentiate into the classic MSC triad, i.e., osteocytes, chondrocytes, and adipocytes. Beyond the regenerative capacity of these cells, studies have shown that pericytes play crucial roles in various pathologies in the lung, both acute (acute respiratory distress syndrome and sepsis-related pulmonary edema) and chronic (pulmonary hypertension, lung tumors, idiopathic pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease). Taken together, this body of evidence suggests that, in the presence of acute and chronic pulmonary inflammation, pericytes are not associated with tissue regeneration and repair, but rather transform into scar-forming myofibroblasts, with devastating outcomes regarding lung structure and function. It is hoped that further studies into the mechanisms of pericyte-to-myofibroblast transition and migration to fibrotic foci will clarify the roles of pericytes in chronic lung disease and open up new avenues in the search for novel treatments for human pulmonary pathologies.", keywords = "Acute respiratory distress syndrome, Asthma, Chronic obstructive pulmonary disease, Edema, Fibrosis, Idiopathic pulmonary hypertension, Lung, Migration, Myofibroblast, Pericyte, Pulmonary hypertension, Tumor, Vasculature", author = "Bushra Shammout and Johnson, {Jill R.}", year = "2019", month = may, day = "31", doi = "10.1007/978-3-030-16908-4_14", language = "English", isbn = "978-3-030-16907-7", series = "Advances in Experimental Medicine and Biology", publisher = "Springer", pages = "299--317", booktitle = "Advances in Experimental Medicine and Biology", address = "Germany", } . Advances in Experimental Medicine and Biology.

The Applicability of Mouse Models to the Study of Human Disease @inbook{e94c86bbd6a642938fb13cd90ef92630, title = "The Applicability of Mouse Models to the Study of Human Disease", abstract = "The laboratory mouse Mus musculus has long been used as a model organism to test hypotheses and treatments related to understanding the mechanisms of disease in humans; however, for these experiments to be relevant, it is important to know the complex ways in which mice are similar to humans and, crucially, the ways in which they differ. In this chapter, an in-depth analysis of these similarities and differences is provided to allow researchers to use mouse models of human disease and primary cells derived from these animal models under the most appropriate and meaningful conditions.Although there are considerable differences between mice and humans, particularly regarding genetics, physiology, and immunology, a more thorough understanding of these differences and their effects on the function of the whole organism will provide deeper insights into relevant disease mechanisms and potential drug targets for further clinical investigation. Using specific examples of mouse models of human lung disease, i.e., asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis, this chapter explores the most salient features of mouse models of human disease and provides a full assessment of the advantages and limitations of these models, focusing on the relevance of disease induction and their ability to replicate critical features of human disease pathophysiology and response to treatment. The chapter concludes with a discussion on the future of using mice in medical research with regard to ethical and technological considerations.", keywords = "Disease, Ethics, Genetics, Immunology, Model, Mouse, Physiology", author = "Kristina Rydell-T{\"o}rm{\"a}nen and Johnson, {Jill R.}", year = "2019", month = feb, day = "21", doi = "10.1007/978-1-4939-9086-3_1", language = "English", isbn = "978-1-4939-9085-6", volume = "1940", series = "Methods in molecular biology (Clifton, N.J.)", publisher = "Springer", pages = "3--22", booktitle = "Mouse Cell Culture", address = "Germany", } . Mouse Cell Culture.

Jill Johnson, E. Cates, R. Fattouh, A. Llop-Guevara, M. Jordana(2007). Modeling responses to respiratory house dust mite exposure . Models of Exacerbations in Asthma and COPD. Microsoft.AspNetCore.Mvc.Localization.LocalizedHtmlString 42--67. Karger

BOOK

Modeling responses to respiratory house dust mite exposure.