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

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.

IL ‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

“…Recently, the local microbiome has emerged to play an important role in the homeostasis of Vγ6 + T cells . To control for the possibility that a unique microbiome in our animal facility affects Vγ6 + T‐cell homeostasis in the ageing cohort, we analysed pLNs from young and old mice housed in a different animal facility and obtained identical results (Appendix Fig S2A–F).…”

IL-17–producing γδ T cells protect against Clostridium difficile infection

“…IL-17 has been implicated in the development of chronic inflammation and autoimmunity. Preclinical infection models show that it is also essential for host defense against bacterial and fungal pathogens and in maintaining homeostasis, particularly at mucoepithelial surfaces (55,84). The dual roles of IL-17 appear to be conserved in humans, as heightened levels of expression have been linked to the development of Crohn's disease and psoriasis, whereas patients genetically deficient in IL17RA or expressing a dominant-negative form of IL17F are susceptible to mucocutaneous candidiasis.…”

Recognition of Candida albicans and Role of Innate Type 17 Immunity in Oral Candidiasis

“…For instance, gingival γδT cells of adult mice are mainly composed of Vγ6+ (~60%) and Vγ1+ (~20%), while other subsets Vγ4+ (~10%), Vγ5+ (~5%) and Vγ7+ (~2%) are less enriched in this area [113]. They reside in the basal layer of the oral epithelium and in the junctional epithelium close to the dental biofilm, where they can reach the suprabasal layers [114]. It was demonstrated that during C. albicans infection in HIV patients the number of Vδ1 T cells was significantly higher when compared to HIV-patients with no infection.…”

“…They play an important role in OPC in mice, although TCR-δ−/− mice are mainly resistant to oral candidiasis [31]. γδ T cells can produce high amounts of IL-17 on a per-cell basis [119,120], and thus are potentially an important source of oral IL-17, which plays a crucial role in OPC [30,114]. Interestingly, the development of uterine γδ T cells in mice was independent from microflora, while Vγ6+ γδT cells in the gingiva were shown to be dependent [114,121].…”