Excess IL-1 signaling enhances the development of Th17 cells by downregulating TGF-β-induced Foxp3 expression

Satoshi Ikeda, Shinobu Saijo, Masanori A. Murayama, Kenji Shimizu, Aoi Akitsu, Yoichiro Iwakura

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

IL-1R antagonist-deficient (Il1rn-/-) mice develop autoimmune arthritis in which IL-17A plays a crucial role. Although many studies have shown that Th17 cell differentiation is dependent on TGF-β and IL-6, we found that Th17 cells developed normally in Il1rn-/-Il6-/- mice in vivo. Then, we analyzed the mechanisms of Th17 cell differentiation in Il1rn-/-Il6-/- mice. We found that IL-21 production was increased in the lymph nodes of Il1rn-/- mice, naive Il6 -/- CD4+ T cells differentiated into Th17 cells when cultured with TGF-β and IL-21, and the differentiation was greatly enhanced when IL-1 was added to the culture. Th17 cell differentiation was not induced by either TGF-β or IL-1 alone or in combination. IL-21 induced IL-1R expression in naive CD4+ T cells, and IL-1 inhibited TGF-β-induced Foxp3 expression, resulting in the promotion of Th17 cell differentiation. Furthermore, IL-1 augmented the expression of Th17 cell-specific transcription factors such as Nfkbiz and Batf. These results indicate that excess IL-1 signaling can overcome the requirement of IL-6 in the differentiation of Th17 cells by suppressing Foxp3 expression and inducing Th17 cell-specific transcription factors.

Original languageEnglish
Pages (from-to)1449-1458
Number of pages10
JournalJournal of Immunology
Volume192
Issue number4
DOIs
Publication statusPublished - 15 Feb 2014

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