Regulating human Th17 cells via differential expression of IL-1 receptor (34.7)

Abstract

Abstract In humans, IL-1β is essential for developing Th17 cells. However, little is known about the relationship of IL-1 receptor (IL-1R) expression and Th17 cell differentiation. We report the presence of two distinct CD4+ T cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in human naive and memory CD4+ T cells. A combination of T cell receptor (TCR) triggering and IL-1β augmented IL-17 production from IL-1RI+ memory CD4+ T cells. IL-1RI+ memory CD4+ T cells in peripheral blood had increased gene expression of IL17, RORC and IRF4 even before TCR triggering, suggesting that the programmed effect of IL-1β in these cells. Of interest, IL-1β also promoted IL-17 production from TCR-stimulated IL-1RI- memory CD4+ T cells, which was likely secondary to TCR-mediated up-regulation of IL-1RI. Adding IL-1β to TCR triggering resulted in production of IL-17 from IL-1RI+ but not from IL-1RI- naive CD4+ T cells. While CD4+ T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15 and TGF-β up-regulated IL-1RI expression on naive CD4+ T cells, suggesting that IL-1RI+ naive CD4+ T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated IL-1R1- naive CD4+ T cells was induced by IL-1β and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI which is controlled by IL-7 and IL-15.