RT Journal Article
SR Electronic
T1 TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101181
DO 10.26508/lsa.202101181
VO 5
IS 2
A1 Yusuke Miyashita
A1 Takahisa Kouwaki
A1 Hirotake Tsukamoto
A1 Masaaki Okamoto
A1 Kimitoshi Nakamura
A1 Hiroyuki Oshiumi
YR 2022
UL https://www.life-science-alliance.org/content/5/2/e202101181.abstract
AB 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-κB 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.