Critical regulation of early Th17 cell differentiation by interleukin-1 signaling

TitleCritical regulation of early Th17 cell differentiation by interleukin-1 signaling
Publication TypeJournal Article
Year of Publication2009
AuthorsChung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich SS, Jetten AM, Tian Q, Dong C
Date PublishedApr 17
PubMed Central ID2705871
Keywords*Cell Differentiation, *Gene Expression Regulation, *Signal Transduction, Animals, Cell Lineage, Interleukin-1/*metabolism, Interleukin-17/metabolism, Mice, Mice, Inbred C57BL, Receptors, Interleukin-1/genetics/metabolism, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger/biosynthesis, T-Lymphocyte Subsets/*cytology/immunology, T-Lymphocytes, Helper-Inducer/*cytology/immunology, Up-Regulation
AbstractT helper (Th) 17 cells have been recently discovered in both mouse and human. Here we show that interleukin-1 (IL-1) signaling on T cells is critically required for the early programming of Th17 cell lineage and Th17 cell-mediated autoimmunity. IL-1 receptor1 expression in T cells, which was induced by IL-6, was necessary for the induction of experimental autoimmune encephalomyelitis and for early Th17 cell differentiation in vivo. Moreover, IL-1 signaling in T cells was required in dendritic cell-mediated Th17 cell differentiation from naive or regulatory precursors and IL-1 synergized with IL-6 and IL-23 to regulate Th17 cell differentiation and maintain cytokine expression in effector Th17 cells. Importantly, IL-1 regulated the expression of the transcription factors IRF4 and RORgammat during Th17 cell differentiation; overexpression of these two factors resulted in IL-1-independent Th17 cell polarization. Our data thus indicate a critical role of IL-1 in Th17 cell differentiation and this pathway may serve as a unique target for Th17 cell-mediated immunopathology.