MAITcells 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. Mucosalassociated 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 MAITcells 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 vs. cervix. The MAIT cells from the FGT and blood displayed a distinct phenotype with expression of interleukin (IL)-18R alpha, CD127, alpha 4 beta 7, PD-1, as well as the transcription factors promyelocytic leukemia zinc finger (PLZF), ROR gamma t, Helios, Eomes, and T-bet. Their expression levels of PLZF and Eomes were lower in the FGT compared with 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-gamma, TNF, and Granzyme B. Furthermore, both FGT-and blood-derived MAITcells were polyfunctional and contributed to the T-cell-mediated response to E. coli. Thus, MAITcells in the genital mucosa have a distinct IL-17/IL-22 profile and may have an important role in the immunological homeostasis and control of microbes at this site.