| First Author | Jin W | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 26 | Pages | 6603-10 |
| PubMed ID | 19411637 | Mgi Jnum | J:150149 |
| Mgi Id | MGI:3849794 | Doi | 10.1182/blood-2008-12-192914 |
| Citation | Jin W, et al. (2009) Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK. Blood 113(26):6603-10 |
| abstractText | 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-kappaB-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. |
