IL-36γ induction in the human female reproductive tract is microbe-dependent (P4009)

Abstract

Abstract The interleukin-1 (IL-1) family consists of pleiotropic cytokines that play a role in the initiation of immune and inflammatory responses. IL-36γ (IL-1F9) is a newly identified IL-1 family member that functions as an agonist. IL-36γ is highly expressed in epithelial cells of the intestine, lungs, and skin, however IL-36γ has not previously been characterized in the human female reproductive tract (FRT). Upon pathogen infection or during inflammatory disorders, IL-36γ is induced and signals through the IL-1R-related protein 2 receptor to trigger NF-κB expression and IL-6 and IL-8 production. Here, we demonstrate for the first time the expression and regulation of IL-36γ in human FRT epithelial cells. Utilizing a human 3-D FRT epithelial cell model previously shown to express functional TLRs similar to in vivo tissue, we demonstrate a unique IL-36γ expression signature upon microbial product stimulation. Treatment of the FRT cells with pathogenic microbial products resulted in a significant increase in IL-36γ expression by quantitative RT-PCR, however exposure of FRT cells to commensal bacteria showed no significant increase in IL-36γ. Induction of IL-36γ by microbial products appears to be TLR dependent. From this data we show for the first time that human 3-D FRT cells express IL-36γ and respond in a microbe-dependent manner. In conclusion, our work begins to elucidate a novel innate immune response mechanism involving IL-36γ induction during FRT mucosal infection.