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

TY - JOUR

T1 - Mutual interplay between IL-17-producing γδT cells and microbiota orchestrates oral mucosal homeostasis

AU - Wilharm, Anneke

AU - Tabib, Yaara

AU - Nassar, Maria

AU - Reinhardt, Annika

AU - Mizraji, Gabriel

AU - Sandrock, Inga

AU - Heyman, Oded

AU - Barros-Martins, Joana

AU - Aizenbud, Yuval

AU - Khalaileh, Abed

AU - Eli-Berchoer, Luba

AU - Elinav, Eran

AU - Wilensky, Asaf

AU - Förster, Reinhold

AU - Bercovier, Herve

AU - Prinz, Immo

AU - Hovav, Avi-Hai

PY - 2019/2/12

Y1 - 2019/2/12

N2 - 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.

AB - 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.

KW - Animals

KW - Biofilms

KW - Gingiva/immunology

KW - Homeostasis

KW - Inflammation/immunology

KW - Interleukin-17/biosynthesis

KW - Mice

KW - Microbiota

KW - Mouth Mucosa/microbiology

KW - Receptors, Antigen, T-Cell, gamma-delta/metabolism

KW - T-Lymphocytes/metabolism

U2 - 10.1073/pnas.1818812116

DO - 10.1073/pnas.1818812116

M3 - SCORING: Journal article

C2 - 30692259

VL - 116

SP - 2652

EP - 2661

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 7

ER -