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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,...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
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.
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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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