Abstract
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.
Highlights
The epithelium of the human female reproductive tract (FRT) plays host to a wide variety of commensal bacteria and acts as a first responder to invading microbes and changes in the microbial milieu
The pattern of cytokine and AMP induction was similar for vaginal and cervical cells and was dose-dependent, but the magnitude was higher in the 3-D vaginal epithelial cells (ECs) model relative to the 3-D cervical model for most immune mediators evaluated. This is the first report demonstrating a role for IL-36γ in host defense and amplification of the mucosal immune response by ECs lining the FRT
We showed that in the lower FRT, IL-36γ stimulates the innate immune response by induction of pro-inflammatory cytokines, chemokines, and AMP, thereby promoting mucosal inflammation
Summary
The epithelium of the human FRT plays host to a wide variety of commensal bacteria and acts as a first responder to invading microbes and changes in the microbial milieu. The human FRT can be divided into two distinct regions that differ in cellular structure and function. The lower FRT epithelium is composed of the vagina and ectocervix and is lined with a stratified squamous epithelium built to resist physical and mechanical stress. The upper FRT epithelium is made up of a single layer of columnar EC and includes the endocervix, endometrium, fallopian tubes, and the uterus (Horne et al, 2008). Site-specific differences in the magnitude and pattern of immune response have been investigated in the vagina and endocervix (Quayle, 2002; Pudney et al, 2005; Herbst-Kralovetz et al, 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
