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IL-33 blockade affe...
IL-33 blockade affects mediators of persistence and exacerbation in a model of chronic airway inflammation
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- Allinne, Jeanne (author)
- Regeneron Pharmaceuticals, Inc.
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- Scott, George (author)
- Regeneron Pharmaceuticals, Inc.
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- Lim, Wei Keat (author)
- Regeneron Pharmaceuticals, Inc.
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- Birchard, Dylan (author)
- Regeneron Pharmaceuticals, Inc.
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- Erjefält, Jonas S. (author)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups,Medetect AB
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- Sandén, Caroline (author)
- Medetect AB
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- Ben, Li Hong (author)
- Regeneron Pharmaceuticals, Inc.
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- Agrawal, Amit (author)
- Regeneron Pharmaceuticals, Inc.
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- Kaur, Navneet (author)
- Regeneron Pharmaceuticals, Inc.
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- Kim, Jee Hae (author)
- Regeneron Pharmaceuticals, Inc.
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- Kamat, Vishal (author)
- Regeneron Pharmaceuticals, Inc.
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- Fury, Wen (author)
- Regeneron Pharmaceuticals, Inc.
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- Huang, Tammy (author)
- Regeneron Pharmaceuticals, Inc.
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- Stahl, Neil (author)
- Regeneron Pharmaceuticals, Inc.
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- Yancopoulos, George D. (author)
- Regeneron Pharmaceuticals, Inc.
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- Murphy, Andrew J. (author)
- Regeneron Pharmaceuticals, Inc.
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- Sleeman, Matthew A. (author)
- Regeneron Pharmaceuticals, Inc.
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- Orengo, Jamie M. (author)
- Regeneron Pharmaceuticals, Inc.
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Regeneron Pharmaceuticals, Inc Luftvägsinflammation (creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English 24 s.
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 144:6, s. 1624-1637
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Abstract
Subject headings
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- Background: Severe inflammatory airway diseases are associated with inflammation that does not resolve, leading to structural changes and an overall environment primed for exacerbations. Objective: We sought to identify and inhibit pathways that perpetuate this heightened inflammatory state because this could lead to therapies that allow for a more quiescent lung that is less predisposed to symptoms and exacerbations. Methods: Using prolonged exposure to house dust mite in mice, we developed a mouse model of persistent and exacerbating airway disease characterized by a mixed inflammatory phenotype. Results: We show that lung IL-33 drives inflammation and remodeling beyond the type 2 response classically associated with IL-33 signaling. IL-33 blockade with an IL-33 neutralizing antibody normalized established inflammation and improved remodeling of both the lung epithelium and lung parenchyma. Specifically, IL-33 blockade normalized persisting and exacerbating inflammatory end points, including eosinophilic, neutrophilic, and ST2+CD4+ T-cell infiltration. Importantly, we identified a key role for IL-33 in driving lung remodeling because anti–IL-33 also re-established the presence of ciliated cells over mucus-producing cells and decreased myofibroblast numbers, even in the context of continuous allergen exposure, resulting in improved lung function. Conclusion: Overall, this study shows that increased IL-33 levels drive a self-perpetuating amplification loop that maintains the lung in a state of lasting inflammation and remodeled tissue primed for exacerbations. Thus IL-33 blockade might ameliorate symptoms and prevent exacerbations by quelling persistent inflammation and airway remodeling.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- airway inflammation
- airway remodeling
- anti–IL-33
- asthma
- exacerbation
- house dust mite
- IL-33
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Allinne, Jeanne
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Scott, George
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Lim, Wei Keat
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Birchard, Dylan
-
Erjefält, Jonas ...
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Sandén, Caroline
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show more...
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Ben, Li Hong
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Agrawal, Amit
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Kaur, Navneet
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Kim, Jee Hae
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Kamat, Vishal
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Fury, Wen
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Huang, Tammy
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Stahl, Neil
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Yancopoulos, Geo ...
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Murphy, Andrew J ...
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Sleeman, Matthew ...
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Orengo, Jamie M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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Journal of Aller ...
- By the university
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Lund University