Details

Autor(en) / Beteiligte

• Chung, Yeonseok
• Chang, Seon Hee
• Martinez, Gustavo J.
• Yang, Xuexian O.
• Nurieva, Roza
• Kang, Hong Soon
• Ma, Li
• Watowich, Stephanie S.
• Jetten, Anton M.
• Tian, Qiang
• Dong, Chen

Titel

Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling

Ist Teil von

• Immunity (Cambridge, Mass.), 2009-04, Vol.30 (4), p.576-587

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 RORγt 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.