MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation

The female genital tract (FGT) mucosa is a critically important site for immune defense against microbes. Mucosal-associated invariant T (MAIT) cells are an innate-like T cell population that recognizes microbial riboflavin metabolite antigens in an MR1-dependent manner. The role of MAIT cells in the FGT mucosa is unknown. Here, we found that MAIT cells and MR1(+) antigen-presenting cells were present in the upper and lower FGT, with distinct tissue localization of MAIT cells in endometrium versus cervix. MAIT cells from the FGT and blood displayed a distinct phenotype with expression of IL-18Rα, CD127, α4β7, PD-1, as well as the transcription factors PLZF, RORγt, Helios, Eomes and T-bet. Their expression levels of PLZF and Eomes were lower in the FGT compared to blood. When stimulated with Escherichia coli, MAIT cells from the FGT displayed a bias towards IL-17 and IL-22 expression, whereas blood MAIT cells produced primarily IFN-γ, TNF, and Granzyme B. Furthermore, both FGT- and blood-derived MAIT cells were polyfunctional and contributed to the T cell-mediated response to E. coli. Thus, MAIT cells in the genital mucosa have a distinct IL-17/IL-22 profile and may play an important role in immunological homeostasis and control of microbes at this site.