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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6603-6610. Prepublished online as a Blood First Edition Paper on May 1, 2009; DOI 10.1182/blood-2008-12-192914. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-12-192914v1 113/26/6603    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Jin, W. Articles by Sun, S.-C. PubMed PubMed Citation Articles by Jin, W. Articles by Sun, S.-C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK Wei Jin1,*, Xiao-Fei Zhou1,*, Jiayi Yu1, Xuhong Cheng1, and Shao-Cong Sun1 1 Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston Th17 cells play an important role in mediating autoimmune diseases, but the molecular mechanism underlying Th17 differentiation is incompletely understood. We show here that NF-B–inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Th17 cells. NIK-deficient naive CD4 T cells are attenuated in the differentiation to Th17 cells, although they are competent in committing to the other effector lineages. Consistently, NIK knockout mice are resistant to experimental autoimmune encephalomyelitis, a disease model that involves the function of Th17 cells. This phenotype was also detected in Rag2 knockout mice reconstituted with NIK-deficient T cells, confirming a T-cell intrinsic defect. We further show that NIK mediates synergistic activation of STAT3 by T-cell receptor and IL-6 receptor signals. NIK deficiency attenuates activation of STAT3 and induction of STAT3 target genes involved in Th17-commitment program. These findings establish NIK as an important signaling factor that regulates Th17 differentiation and experimental autoimmune encephalitis induction. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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