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

• Published in: Mucosal immunology Vol. 10; no. 1; pp. 35 - 45
• Main Authors: Gibbs, A., Leeansyah, E., Introini, A., Paquin-Proulx, D., Hasselrot, K., Andersson, E., Broliden, K., Sandberg, J.K., Tjernlund, A.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.01.2017; Nature Publishing Group US; Elsevier Limited
• Subjects: 631/250/1619/554; 631/250/21/1293; 631/250/347; 631/326/41/2533; Adult; Allergology; Antibodies; Antigens, Bacterial - immunology; article-report; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Cervix Uteri - immunology; Cervix Uteri - pathology; Endometrium - immunology; Endometrium - pathology; Escherichia coli - immunology; Female; Gastroenterology; Histocompatibility Antigens Class I - metabolism; Humans; Immunity, Innate; Immunology; Interleukin-17 - metabolism; Interleukin-22; Interleukin-7 Receptor alpha Subunit - metabolism; Interleukins - metabolism; Middle Aged; Minor Histocompatibility Antigens - metabolism; Mucous Membrane - immunology; Natural Killer T-Cells - immunology; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Riboflavin - immunology
• DOI: 10.1038/mi.2016.30
• ISSN: 1933-0219

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 vs. cervix. The MAIT cells from the FGT and blood displayed a distinct phenotype with expression of interleukin (IL)-18Rα, CD127, α4β7, PD-1, as well as the transcription factors promyelocytic leukemia zinc finger (PLZF), RORγt, 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-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 have an important role in the immunological homeostasis and control of microbes at this site.