γδ T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis
Leticia Monin, Dmitry S. Ushakov, Henriette Arnesen, Nourdine Bah, Anett Jandke, Miguel Muñoz‐Ruiz, Joana Carvalho, Susan Joseph, Bruna Almeida, Mary Green, Emma Nye, Shinya Hatano, Yasunobu Yoshikai, Michael A. Curtis, Harald Carlsen, Ulrich Steinhoff, Preben Boysen, Adrian Hayday
Abstract
This most comprehensive analysis to date of γδ T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1 + T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-Vγ6 + , IFN-γ-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, γδ T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans , associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal γδ cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.