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

Mucosal Immunol. 2017 Jan;10(1):35-45. doi: 10.1038/mi.2016.30. Epub 2016 Apr 6.

Abstract

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.

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology*
  • Cells, Cultured
  • Cervix Uteri / immunology*
  • Cervix Uteri / pathology
  • Endometrium / immunology*
  • Endometrium / pathology
  • Escherichia coli / immunology*
  • Female
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity, Innate*
  • Interleukin-17 / metabolism
  • 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

Substances

  • Antigens, Bacterial
  • Histocompatibility Antigens Class I
  • Interleukin-17
  • Interleukin-7 Receptor alpha Subunit
  • Interleukins
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Riboflavin
  • interleukin-22