IL-17 Production by γδ + T Cells Is Critical for Inducing T h 17 Responses in the Female Genital Tract and Regulated by Estradiol and Microbiota

Immunohorizons. 2019 Jul 17;3(7):317-330. doi: 10.4049/immunohorizons.1900040.

Abstract

IL-17 can be produced by adaptive immune cells such as Th17 cells and by immune cells that produce IL-17 without prior priming. This latter category, which we will refer to as "innate," includes innate cells such as NK cells and innate lymphoid cells and innate-like T cell populations such as NKT cells and γδ+ T cells. Studies in mucosal tissues have shown that the induction of Th17 immunity is amplified by innate IL-17 produced within those tissues. However, the role of innate IL-17 and its effect on Th17 induction in the female genital tract (FGT) is largely unknown. In this study, we characterize the primary source of IL-17-secreting vaginal cells and show that innate IL-17 plays a critical role in priming adaptive Th17 responses in the FGT. Under homeostatic conditions, γδ+ T cells were the predominant source of innate IL-17 in the murine FGT, and this population was modulated by both the sex hormone estradiol and the presence of commensal microbiota. Compared with wild-type C57BL/6 mice, vaginal APCs isolated from IL-17A-deficient (IL-17A-/- ) mice were severely impaired at priming Th17 responses in APC-T cell cocultures. Furthermore, the defect in Th17 induction in the absence of innate IL-17 was associated with impairment of IL-1β production by vaginal CD11c+ dendritic cells. Overall, our study describes a novel role for IL-17 in the FGT and further demonstrates the importance of factors in the vaginal microenvironment that can influence adaptive immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Antigen-Presenting Cells / immunology
  • CD11 Antigens / metabolism
  • Dendritic Cells / immunology
  • Estradiol / immunology*
  • Estradiol / pharmacology
  • Female
  • Gene Knockout Techniques
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / immunology
  • Immunity, Innate / immunology
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-1beta / biosynthesis
  • Intraepithelial Lymphocytes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota / immunology*
  • Th17 Cells / immunology*
  • Vagina / cytology*

Substances

  • CD11 Antigens
  • IL1B protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-1beta
  • Itgax protein, mouse
  • Estradiol

Grant support