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Mutual interplay between IL-17-producing ??T cells and microbiota orchestrates oral mucosal homeostasis.


ABSTRACT: ??T cells are a major component of epithelial tissues and play a role in tissue homeostasis and host defense. ??T cells also reside in the gingiva, an oral tissue covered with specialized epithelium that continuously monitors the challenging dental biofilm. Whereas most research on intraepithelial ??T cells focuses on the skin and intestine epithelia, our knowledge on these cells in the gingiva is still incomplete. In this study, we demonstrate that even though the gingiva develops after birth, the majority of gingival ??T cells are fetal thymus-derived V?6+ cells, and to a lesser extent V?1+ and V?4+ cells. Furthermore, we show that ??T cells are motile and locate preferentially in the epithelium adjacent to the biofilm. V?6+ cells represent the major source of IL-17-producing cells in the gingiva. Chimeric mice and parabiosis experiments indicated that the main fraction of gingival ??T cells is radioresistant and tissue-resident, persisting locally independent of circulating ??T cells. Notably, gingival ??T cell homeostasis is regulated by the microbiota as the ratio of V?6+ and V?4+ cells was reversed in germ-free mice, and their activation state was decreased. As a consequence, conditional ablation of ??T cells results in elevated gingival inflammation and subsequent alterations of oral microbial diversity. Taken together, these findings suggest that oral mucosal homeostasis is shaped by reciprocal interplays between ??T cells and local microbiota.

SUBMITTER: Wilharm A 

PROVIDER: S-EPMC6377488 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Mutual interplay between IL-17-producing γδT cells and microbiota orchestrates oral mucosal homeostasis.

Wilharm Anneke A   Tabib Yaara Y   Nassar Maria M   Reinhardt Annika A   Mizraji Gabriel G   Sandrock Inga I   Heyman Oded O   Barros-Martins Joana J   Aizenbud Yuval Y   Khalaileh Abed A   Eli-Berchoer Luba L   Elinav Eran E   Wilensky Asaf A   Förster Reinhold R   Bercovier Herve H   Prinz Immo I   Hovav Avi-Hai AH  

Proceedings of the National Academy of Sciences of the United States of America 20190128 7


γδT cells are a major component of epithelial tissues and play a role in tissue homeostasis and host defense. γδT cells also reside in the gingiva, an oral tissue covered with specialized epithelium that continuously monitors the challenging dental biofilm. Whereas most research on intraepithelial γδT cells focuses on the skin and intestine epithelia, our knowledge on these cells in the gingiva is still incomplete. In this study, we demonstrate that even though the gingiva develops after birth,  ...[more]

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