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

Anneke Wilharm, Yaara Tabib, Maria Nassar, Annika Reinhardt, Gabriel Mizraji, Inga Sandrock, Oded Heyman, Joana Barros-Martins, Yuval Aizenbud, Abed Khalaileh, Luba Eli-Berchoer, Eran Elinav, Asaf Wilensky, Reinhold Förster, Herve Bercovier, Immo Prinz, Avi Hai Hovav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

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, the majority of gingival γδT cells are fetal thymus-derived Vγ6 + cells, and to a lesser extent Vγ1 + and Vγ4 + cells. Furthermore, we show that γδT cells are motile and locate preferentially in the epithelium adjacent to the biofilm. Vγ6 + 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 γδT cells is radioresistant and tissue-resident, persisting locally independent of circulating γδT cells. Notably, gingival γδT cell homeostasis is regulated by the microbiota as the ratio of Vγ6 + and Vγ4 + cells was reversed in germ-free mice, and their activation state was decreased. As a consequence, conditional ablation of γδT 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 γδT cells and local microbiota.

Original languageAmerican English
Pages (from-to)2652-2661
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number7
DOIs
StatePublished - 12 Feb 2019

Bibliographical note

Publisher Copyright:
© 2019 National Academy of Sciences. All Rights Reserved.

Keywords

  • Gingiva
  • Microbiota
  • Oral mucosa
  • Vγ6
  • ΓδT cells

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