| First Author | Jiang Y | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 921 | PubMed ID | 29760709 |
| Mgi Jnum | J:311859 | Mgi Id | MGI:6780983 |
| Doi | 10.3389/fimmu.2018.00921 | Citation | Jiang Y, et al. (2018) Protein Kinase Serine/Threonine Kinase 24 Positively Regulates Interleukin 17-Induced Inflammation by Promoting IKK Complex Activation. Front Immunol 9:921 |
| abstractText | Interleukin 17 (IL-17) is a key inflammatory cytokine that plays a critical role in tissue inflammation and autoimmune diseases. However, its signaling remains poorly understood. In this study, we identified serine/threonine kinase 24 (Stk24) as a positive modulator of IL-17-mediated signaling and inflammation. Stk24 deficiency or knockdown markedly inhibited IL-17-induced phosphorylation of NF-kappaB and impaired IL-17-induced chemokines and cytokines expression. Stk24 overexpression greatly enhanced IL-17-induced NF-kappaB activation and expression of chemokines and cytokines in a kinase activity-independent manner. The IL-17-induced inflammatory response was significantly reduced in Stk24-deficient mice. In addition, the severity of experimental autoimmune encephalomyelitis was markedly reduced in mice with a deficiency of Stk24 in non-hematopoietic cells. We further demonstrated that Stk24 directly interacts with TAK1 and IKKbeta and promotes the formation of TAK1/IKK complexes, leading to enhanced IKKbeta/NF-kappaB activation and downstream cytokines and chemokines induction. Collectively, our findings suggest that Stk24 plays an important role in controlling IL-17-triggered inflammation and autoimmune diseases and provides new insight into the therapeutic targets of IL-17-mediated inflammatory disease. |
