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

First Author  Wilharm A Year  2019
Journal  Proc Natl Acad Sci U S A Volume  116
Issue  7 Pages  2652-2661
PubMed ID  30692259 Mgi Jnum  J:272502
Mgi Id  MGI:6280551 Doi  10.1073/pnas.1818812116
Citation  Wilharm A, et al. (2019) Mutual interplay between IL-17-producing gammadeltaT cells and microbiota orchestrates oral mucosal homeostasis. Proc Natl Acad Sci U S A 116(7):2652-2661
abstractText  gammadeltaT cells are a major component of epithelial tissues and play a role in tissue homeostasis and host defense. gammadeltaT 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 gammadeltaT 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 gammadeltaT cells are fetal thymus-derived Vgamma6(+) cells, and to a lesser extent Vgamma1(+) and Vgamma4(+) cells. Furthermore, we show that gammadeltaT cells are motile and locate preferentially in the epithelium adjacent to the biofilm. Vgamma6(+) 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 gammadeltaT cells is radioresistant and tissue-resident, persisting locally independent of circulating gammadeltaT cells. Notably, gingival gammadeltaT cell homeostasis is regulated by the microbiota as the ratio of Vgamma6(+) and Vgamma4(+) cells was reversed in germ-free mice, and their activation state was decreased. As a consequence, conditional ablation of gammadeltaT 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 gammadeltaT cells and local microbiota.
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