| Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. | |
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MedLine Citation:
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PMID: 20802484 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Severe asthma is associated with the production of interleukin 17A (IL-17A). The exact role of IL-17A in severe asthma and the factors that drive its production are unknown. Here we demonstrate that IL-17A mediated severe airway hyperresponsiveness (AHR) in susceptible strains of mice by enhancing IL-13-driven responses. Mechanistically, we demonstrate that IL-17A and AHR were regulated by allergen-driven production of anaphylatoxins, as mouse strains deficient in complement factor 5 (C5) or the complement receptor C5aR mounted robust IL-17A responses, whereas mice deficient in C3aR had fewer IL-17-producing helper T cells (T(H)17 cells) and less AHR after allergen challenge. The opposing effects of C3a and C5a were mediated through their reciprocal regulation of IL-23 production. These data demonstrate a critical role for complement-mediated regulation of the IL-23-T(H)17 axis in severe asthma. |
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Authors:
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Stephane Lajoie; Ian P Lewkowich; Yusuke Suzuki; Jennifer R Clark; Alyssa A Sproles; Krista Dienger; Alison L Budelsky; Marsha Wills-Karp |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-29 |
Journal Detail:
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Title: Nature immunology Volume: 11 ISSN: 1529-2916 ISO Abbreviation: Nat. Immunol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-21 Completed Date: 2010-11-03 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 100941354 Medline TA: Nat Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 928-35 Citation Subset: IM |
Affiliation:
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Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Allergens
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adverse effects Anaphylatoxins / biosynthesis Animals Asthma / genetics, immunology* Complement Activation Complement C3a / genetics, immunology* Complement C5a / genetics, immunology* Cytokines / biosynthesis Genetic Predisposition to Disease Interleukin-13 / biosynthesis Interleukin-17 / biosynthesis*, genetics Interleukin-23 / immunology* Male Mice Mice, Inbred AKR Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Pyroglyphidae / immunology Receptor, Anaphylatoxin C5a / genetics Th2 Cells / immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI083315/AI/NIAID NIH HHS; AR47363/AR/NIAMS NIH HHS; HL67736/HL/NHLBI NIH HHS; P50 ES015903-010004/ES/NIEHS NIH HHS; P50ES015903/ES/NIEHS NIH HHS; R01 AI083315-03/AI/NIAID NIH HHS; R01 HL067736-09/HL/NHLBI NIH HHS; R01 HL067736-10/HL/NHLBI NIH HHS; U19 AI070235-040003/AI/NIAID NIH HHS; U19A1070235//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Allergens; 0/Anaphylatoxins; 0/Cytokines; 0/Interleukin-13; 0/Interleukin-17; 0/Interleukin-23; 0/Receptor, Anaphylatoxin C5a; 80295-42-7/Complement C3a; 80295-54-1/Complement C5a |
| Comments/Corrections | |
Comment In:
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Nat Rev Immunol. 2010 Oct;10(10):676
[PMID:
20879164
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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