Critical regulation of early Th17 cell differentiation by interleukin-1 signaling.
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.
Department of Immunology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Yeonseok
Y
Chung
Seon Hee
SH
Chang
Gustavo J
GJ
Martinez
Xuexian O
XO
Yang
Roza
R
Nurieva
Hong Soon
HS
Kang
Li
L
Ma
Stephanie S
SS
Watowich
Anton M
AM
Jetten
Qiang
Q
Tian
Chen
C
Dong
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology; D015854:Up-Regulation
D007375:Interleukin-1; D020381:Interleukin-17; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1