IL-36γ augments host defense and immune responses in human female reproductive tract epithelial cells

Sean M. Winkle, Andrea L. Throop, Melissa M. Herbst-Kralovetz

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


IL-36γ is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36γ in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36γ and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36γ in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36γ treatment resulted in self-amplification of IL-36γ and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36γ are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36γ is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT.

Original languageEnglish (US)
Article number955
JournalFrontiers in Microbiology
Issue numberJUN
StatePublished - 2016


  • Antimicrobial peptides
  • Human epithelial cells
  • IL-1 family
  • IL-36 receptor
  • IL-36γ
  • Inflammatory mediators
  • Innate immunity
  • Microbial products

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)


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