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T 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.