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

Won Woo Lee, Seong Wook Kang, Jihoon Choi, Seung Hyun Lee, Kamini Shah, Elizabeth E. Eynon, Richard A. Flavell, Insoo Kang

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

In humans, interleukin-1β (IL-1β) has been suggested as an essential cytokine for developing IL-17- or IL-17A-producing CD4+ T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4+ T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4+ T cells of human peripheral blood. IL-1RI+ memory CD4+ T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1β is programmed in these cells via IL-1RI. Although CD4+ T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-β (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 naiveCD4+ 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.

Original languageEnglish
Pages (from-to)530-540
Number of pages11
JournalBlood
Volume115
Issue number3
DOIs
StatePublished - 21 Jan 2010

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