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Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis
γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis,...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196490/ https://www.ncbi.nlm.nih.gov/pubmed/30279177 http://dx.doi.org/10.1073/pnas.1802320115 |
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author | Krishnan, Siddharth Prise, Ian E. Wemyss, Kelly Schenck, Louis P. Bridgeman, Hayley M. McClure, Flora A. Zangerle-Murray, Tamsin O’Boyle, Conor Barbera, Thomas A. Mahmood, Faiza Bowdish, Dawn M. E. Zaiss, Dietmar M. W. Grainger, John R. Konkel, Joanne E. |
author_facet | Krishnan, Siddharth Prise, Ian E. Wemyss, Kelly Schenck, Louis P. Bridgeman, Hayley M. McClure, Flora A. Zangerle-Murray, Tamsin O’Boyle, Conor Barbera, Thomas A. Mahmood, Faiza Bowdish, Dawn M. E. Zaiss, Dietmar M. W. Grainger, John R. Konkel, Joanne E. |
author_sort | Krishnan, Siddharth |
collection | PubMed |
description | γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology in murine models of the oral inflammatory disease periodontitis. Alterations in bacterial communities could not account for the increased disease severity seen in γδ T cell-deficient mice. Instead, gingival γδ T cells produced the wound healing associated cytokine amphiregulin, administration of which rescued the elevated oral pathology of tcrδ(−/−) mice. Collectively, our results identify γδ T cells as critical constituents of the immuno-surveillance network that safeguard gingival tissue homeostasis. |
format | Online Article Text |
id | pubmed-6196490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-61964902018-10-23 Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis Krishnan, Siddharth Prise, Ian E. Wemyss, Kelly Schenck, Louis P. Bridgeman, Hayley M. McClure, Flora A. Zangerle-Murray, Tamsin O’Boyle, Conor Barbera, Thomas A. Mahmood, Faiza Bowdish, Dawn M. E. Zaiss, Dietmar M. W. Grainger, John R. Konkel, Joanne E. Proc Natl Acad Sci U S A Biological Sciences γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology in murine models of the oral inflammatory disease periodontitis. Alterations in bacterial communities could not account for the increased disease severity seen in γδ T cell-deficient mice. Instead, gingival γδ T cells produced the wound healing associated cytokine amphiregulin, administration of which rescued the elevated oral pathology of tcrδ(−/−) mice. Collectively, our results identify γδ T cells as critical constituents of the immuno-surveillance network that safeguard gingival tissue homeostasis. National Academy of Sciences 2018-10-16 2018-10-02 /pmc/articles/PMC6196490/ /pubmed/30279177 http://dx.doi.org/10.1073/pnas.1802320115 Text en Copyright © 2018 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Krishnan, Siddharth Prise, Ian E. Wemyss, Kelly Schenck, Louis P. Bridgeman, Hayley M. McClure, Flora A. Zangerle-Murray, Tamsin O’Boyle, Conor Barbera, Thomas A. Mahmood, Faiza Bowdish, Dawn M. E. Zaiss, Dietmar M. W. Grainger, John R. Konkel, Joanne E. Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis |
title | Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis |
title_full | Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis |
title_fullStr | Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis |
title_full_unstemmed | Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis |
title_short | Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis |
title_sort | amphiregulin-producing γδ t cells are vital for safeguarding oral barrier immune homeostasis |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196490/ https://www.ncbi.nlm.nih.gov/pubmed/30279177 http://dx.doi.org/10.1073/pnas.1802320115 |
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