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PMID: 17885690 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice.

The Journal of clinical investigation ·Vol. 117 ·No. 10 ·2007-10-00 ·Pages 2941-51

Wilson MS, Elnekave E, Mentink-Kane MM, Hodges MG, Pesce JT, Ramalingam TR, Thompson RW, Kamanaka M, Flavell RA, Keane-Myers A, Cheever AW, Wynn TA

Abstract

Development of persistent Th2 responses in asthma and chronic helminth infections are a major health concern. IL-10 has been identified as a critical regulator of Th2 immunity, but mechanisms for controlling Th2 effector function remain unclear. IL-10 also has paradoxical effects on Th2-associated pathology, with IL-10 deficiency resulting in increased Th2-driven inflammation but also reduced airway hyperreactivity (AHR), mucus hypersecretion, and fibrosis. We demonstrate that increased IL-13 receptor alpha 2 (IL-13Ralpha2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10(-/-) mice. Using models of allergic asthma and chronic helminth infection, we demonstrate that IL-10 and IL-13Ralpha2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant antiinflammatory mediator, studies with double IL-10/IL-13Ralpha2-deficient mice illustrate an indispensable role for IL-13Ralpha2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13Ralpha2 are both required to control chronic Th2-driven pathological responses.

MeSH Terms
Animals Asthma/genetics,immunology,pathology Bronchial Hyperreactivity/genetics,immunology,pathology Bronchitis/genetics,immunology,pathology Fibrosis Granuloma/genetics,immunology,pathology Interleukin-10/genetics,physiology Interleukin-13 Receptor alpha2 Subunit/genetics,physiology Mice Mice, Mutant Strains Mucus/metabolism Th1 Cells/immunology Th2 Cells/immunology
Chemicals
Interleukin-13 Receptor alpha2 Subunit Interleukin-10
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Wilson Mark S
Immunopathogenesis Section, Laboratory of Parasitic Diseases, and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
Elnekave Eldad
Mentink-Kane Margaret M
Hodges Marcus G
Pesce John T
Ramalingam Thirumalai R
Thompson Robert W
Kamanaka Masahito
Flavell Richard A
Keane-Myers Andrea
Cheever Allen W
Wynn Thomas A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI31546
Published
2007-10-00
Pages
2941-51
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1978425
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1172/JCI31546 PMC Full Text View journal details
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