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γδ T cells protect against lung fibrosis via IL-22
Inflammation-induced pulmonary fibrosis (PF) leads to irreversible loss of lung function and is a predictor of mortality in numerous lung diseases. Why some subjects with lung inflammation but not others develop PF is unclear. In a mouse model of hypersensitivity pneumonitis that progresses to lung...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947077/ https://www.ncbi.nlm.nih.gov/pubmed/20855496 http://dx.doi.org/10.1084/jem.20100061 |
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author | Simonian, Philip L. Wehrmann, Fabian Roark, Christina L. Born, Willi K. O'Brien, Rebecca L. Fontenot, Andrew P. |
author_facet | Simonian, Philip L. Wehrmann, Fabian Roark, Christina L. Born, Willi K. O'Brien, Rebecca L. Fontenot, Andrew P. |
author_sort | Simonian, Philip L. |
collection | PubMed |
description | Inflammation-induced pulmonary fibrosis (PF) leads to irreversible loss of lung function and is a predictor of mortality in numerous lung diseases. Why some subjects with lung inflammation but not others develop PF is unclear. In a mouse model of hypersensitivity pneumonitis that progresses to lung fibrosis upon repeated exposure to the ubiquitous microorganism Bacillus subtilis, γδ T cells expand in the lung and inhibit collagen deposition. We show that a subset of these γδ cells represents the predominant source of the Th17 cytokine IL-22 in this model. Preventing expression of IL-22, either by mutating the aryl hydrocarbon receptor (AhR) or inhibiting AhR signaling, accelerated lung fibrosis. Direct blockade of IL-22 also enhanced collagen deposition in the lung, whereas administration of recombinant IL-22 inhibited lung fibrosis. Moreover, the presence of protective γδ T cells and IL-22 diminished recruitment of CD4(+) T cells to lung. These data reveal a protective pathway that involves the inhibition of αβ T cells by regulatory IL-22–secreting γδ T cells. |
format | Text |
id | pubmed-2947077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29470772011-03-27 γδ T cells protect against lung fibrosis via IL-22 Simonian, Philip L. Wehrmann, Fabian Roark, Christina L. Born, Willi K. O'Brien, Rebecca L. Fontenot, Andrew P. J Exp Med Article Inflammation-induced pulmonary fibrosis (PF) leads to irreversible loss of lung function and is a predictor of mortality in numerous lung diseases. Why some subjects with lung inflammation but not others develop PF is unclear. In a mouse model of hypersensitivity pneumonitis that progresses to lung fibrosis upon repeated exposure to the ubiquitous microorganism Bacillus subtilis, γδ T cells expand in the lung and inhibit collagen deposition. We show that a subset of these γδ cells represents the predominant source of the Th17 cytokine IL-22 in this model. Preventing expression of IL-22, either by mutating the aryl hydrocarbon receptor (AhR) or inhibiting AhR signaling, accelerated lung fibrosis. Direct blockade of IL-22 also enhanced collagen deposition in the lung, whereas administration of recombinant IL-22 inhibited lung fibrosis. Moreover, the presence of protective γδ T cells and IL-22 diminished recruitment of CD4(+) T cells to lung. These data reveal a protective pathway that involves the inhibition of αβ T cells by regulatory IL-22–secreting γδ T cells. The Rockefeller University Press 2010-09-27 /pmc/articles/PMC2947077/ /pubmed/20855496 http://dx.doi.org/10.1084/jem.20100061 Text en © 2010 Simonian 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/). |
spellingShingle | Article Simonian, Philip L. Wehrmann, Fabian Roark, Christina L. Born, Willi K. O'Brien, Rebecca L. Fontenot, Andrew P. γδ T cells protect against lung fibrosis via IL-22 |
title | γδ T cells protect against lung fibrosis via IL-22 |
title_full | γδ T cells protect against lung fibrosis via IL-22 |
title_fullStr | γδ T cells protect against lung fibrosis via IL-22 |
title_full_unstemmed | γδ T cells protect against lung fibrosis via IL-22 |
title_short | γδ T cells protect against lung fibrosis via IL-22 |
title_sort | γδ t cells protect against lung fibrosis via il-22 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947077/ https://www.ncbi.nlm.nih.gov/pubmed/20855496 http://dx.doi.org/10.1084/jem.20100061 |
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