| First Author | Miyashita Y | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 2 | PubMed ID | 34819358 |
| Mgi Jnum | J:316442 | Mgi Id | MGI:6833603 |
| Doi | 10.26508/lsa.202101181 | Citation | Miyashita Y, et al. (2022) TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor-mediated inflammatory responses. Life Sci Alliance 5(2) |
| abstractText | TICAM-1 (also called TRIF) is the sole adaptor of TLR3 that recognizes double-stranded RNA. Here, we report that TICAM-1 is involved not only in TLR3 signaling but also in the cytokine receptor IL-17RA signaling. We found that TICAM-1 bound to IL-17R adaptor Act1 to inhibit the interaction between IL-17RA and Act1. Interestingly, TICAM-1 knockout promoted IL-17RA/Act1 interaction and increased IL-17A-mediated activation of NF-kappaB and MAP kinases, leading to enhanced expression of inflammatory cytokines and chemokines upon IL-17A stimulation. Moreover, Ticam-1 knockout augmented IL-17A-mediated CXCL1 and CXCL2 expression in vivo, resulting in accumulation of myeloid cells. Furthermore, Ticam-1 knockout enhanced delayed type hypersensitivity and exacerbated experimental autoimmune encephalomyelitis. Ticam-1 knockout promoted accumulation of myeloid and lymphoid cells in the spinal cord of EAE-induced mice. Collectively, these data indicate that TICAM-1 inhibits the interaction between IL-17RA and Act1 and functions as a negative regulator in IL-17A-mediated inflammatory responses. |
