https://scholars.lib.ntu.edu.tw/handle/123456789/634492
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Lin, You-Sheng | en_US |
dc.contributor.author | Chang, Yung-Chi | en_US |
dc.contributor.author | TAI-LING CHAO | en_US |
dc.contributor.author | Tsai, Ya-Min | en_US |
dc.contributor.author | Jhuang, Shu-Jhen | en_US |
dc.contributor.author | Ho, Yu-Hsin | en_US |
dc.contributor.author | Lai, Ting-Yu | en_US |
dc.contributor.author | Liu, Yi-Ling | en_US |
dc.contributor.author | Chen, Chiung-Ya | en_US |
dc.contributor.author | Tsai, Ching-Yen | en_US |
dc.contributor.author | Hsueh, Yi-Ping | en_US |
dc.contributor.author | SUI-YUAN CHANG | en_US |
dc.contributor.author | Chuang, Tsung-Hsien | en_US |
dc.contributor.author | CHIH-YUAN LEE | en_US |
dc.contributor.author | LI-CHUNG HSU | en_US |
dc.date.accessioned | 2023-08-09T07:13:18Z | - |
dc.date.available | 2023-08-09T07:13:18Z | - |
dc.date.issued | 2023-08-07 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.issn | 1540-9538 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/634492 | - |
dc.description.abstract | Type I interferons are important antiviral cytokines, but prolonged interferon production is detrimental to the host. The TLR3-driven immune response is crucial for mammalian antiviral immunity, and its intracellular localization determines induction of type I interferons; however, the mechanism terminating TLR3 signaling remains obscure. Here, we show that the E3 ubiquitin ligase ZNRF1 controls TLR3 sorting into multivesicular bodies/lysosomes to terminate signaling and type I interferon production. Mechanistically, c-Src kinase activated by TLR3 engagement phosphorylates ZNRF1 at tyrosine 103, which mediates K63-linked ubiquitination of TLR3 at lysine 813 and promotes TLR3 lysosomal trafficking and degradation. ZNRF1-deficient mice and cells are resistant to infection by encephalomyocarditis virus and SARS-CoV-2 because of enhanced type I interferon production. However, Znrf1-/- mice have exacerbated lung barrier damage triggered by antiviral immunity, leading to enhanced susceptibility to respiratory bacterial superinfections. Our study highlights the c-Src-ZNRF1 axis as a negative feedback mechanism controlling TLR3 trafficking and the termination of TLR3 signaling. | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | The Journal of experimental medicine | en_US |
dc.title | The Src-ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1084/jem.20220727 | - |
dc.identifier.pmid | 37158982 | - |
dc.identifier.scopus | 2-s2.0-85159727903 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/85159727903 | - |
dc.relation.journalvolume | 220 | en_US |
dc.relation.journalissue | 8 | en_US |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Clinical Laboratory Sciences and Medical Biotechnology | - |
crisitem.author.dept | Clinical Laboratory Sciences and Medical Biotechnology | - |
crisitem.author.dept | Laboratory Medicine-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Molecular Medicine | - |
crisitem.author.dept | Immunology | - |
crisitem.author.orcid | 0000-0002-9815-6702 | - |
crisitem.author.orcid | 0000-0002-6009-6724 | - |
crisitem.author.orcid | 0000-0001-5034-3544 | - |
crisitem.author.orcid | 0000-0001-7206-5231 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學檢驗暨生物技術學系 |
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