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Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response

Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-...

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Autores principales: Chiaramonte, Monica G., Mentink-Kane, Margaret, Jacobson, Bruce A., Cheever, Allen W., Whitters, Matthew J., Goad, Mary E.P., Wong, Anthony, Collins, Mary, Donaldson, Debra D., Grusby, Michael J., Wynn, Thomas A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193852/
https://www.ncbi.nlm.nih.gov/pubmed/12642601
http://dx.doi.org/10.1084/jem.20020903
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author Chiaramonte, Monica G.
Mentink-Kane, Margaret
Jacobson, Bruce A.
Cheever, Allen W.
Whitters, Matthew J.
Goad, Mary E.P.
Wong, Anthony
Collins, Mary
Donaldson, Debra D.
Grusby, Michael J.
Wynn, Thomas A.
author_facet Chiaramonte, Monica G.
Mentink-Kane, Margaret
Jacobson, Bruce A.
Cheever, Allen W.
Whitters, Matthew J.
Goad, Mary E.P.
Wong, Anthony
Collins, Mary
Donaldson, Debra D.
Grusby, Michael J.
Wynn, Thomas A.
author_sort Chiaramonte, Monica G.
collection PubMed
description Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)α2 is a critical down-regulatory factor of IL-13–mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13Rα2 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL/6 and BALB/c IL-13Rα2–deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13Rα2–deficient mice were treated with a soluble IL-13Rα2-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13Rα2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response.
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spelling pubmed-21938522008-04-11 Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response Chiaramonte, Monica G. Mentink-Kane, Margaret Jacobson, Bruce A. Cheever, Allen W. Whitters, Matthew J. Goad, Mary E.P. Wong, Anthony Collins, Mary Donaldson, Debra D. Grusby, Michael J. Wynn, Thomas A. J Exp Med Article Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)α2 is a critical down-regulatory factor of IL-13–mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13Rα2 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL/6 and BALB/c IL-13Rα2–deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13Rα2–deficient mice were treated with a soluble IL-13Rα2-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13Rα2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response. The Rockefeller University Press 2003-03-17 /pmc/articles/PMC2193852/ /pubmed/12642601 http://dx.doi.org/10.1084/jem.20020903 Text en Copyright © 2003, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Chiaramonte, Monica G.
Mentink-Kane, Margaret
Jacobson, Bruce A.
Cheever, Allen W.
Whitters, Matthew J.
Goad, Mary E.P.
Wong, Anthony
Collins, Mary
Donaldson, Debra D.
Grusby, Michael J.
Wynn, Thomas A.
Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response
title Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response
title_full Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response
title_fullStr Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response
title_full_unstemmed Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response
title_short Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response
title_sort regulation and function of the interleukin 13 receptor α 2 during a t helper cell type 2–dominant immune response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193852/
https://www.ncbi.nlm.nih.gov/pubmed/12642601
http://dx.doi.org/10.1084/jem.20020903
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