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TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses
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 I...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616538/ https://www.ncbi.nlm.nih.gov/pubmed/34819358 http://dx.doi.org/10.26508/lsa.202101181 |
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author | Miyashita, Yusuke Kouwaki, Takahisa Tsukamoto, Hirotake Okamoto, Masaaki Nakamura, Kimitoshi Oshiumi, Hiroyuki |
author_facet | Miyashita, Yusuke Kouwaki, Takahisa Tsukamoto, Hirotake Okamoto, Masaaki Nakamura, Kimitoshi Oshiumi, Hiroyuki |
author_sort | Miyashita, Yusuke |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8616538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-86165382021-12-09 TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses Miyashita, Yusuke Kouwaki, Takahisa Tsukamoto, Hirotake Okamoto, Masaaki Nakamura, Kimitoshi Oshiumi, Hiroyuki Life Sci Alliance Research Articles 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. Life Science Alliance LLC 2021-11-24 /pmc/articles/PMC8616538/ /pubmed/34819358 http://dx.doi.org/10.26508/lsa.202101181 Text en © 2021 Miyashita et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Miyashita, Yusuke Kouwaki, Takahisa Tsukamoto, Hirotake Okamoto, Masaaki Nakamura, Kimitoshi Oshiumi, Hiroyuki TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses |
title | TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses |
title_full | TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses |
title_fullStr | TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses |
title_full_unstemmed | TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses |
title_short | TICAM-1/TRIF associates with Act1 and suppresses IL-17 receptor–mediated inflammatory responses |
title_sort | ticam-1/trif associates with act1 and suppresses il-17 receptor–mediated inflammatory responses |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616538/ https://www.ncbi.nlm.nih.gov/pubmed/34819358 http://dx.doi.org/10.26508/lsa.202101181 |
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