{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:43:08Z","timestamp":1792014188997,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013333","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472293"],"award-info":[{"award-number":["82472293"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82125021"],"award-info":[{"award-number":["82125021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82321002"],"award-info":[{"award-number":["82321002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cutting Edge Development Fund of Advanced Medical Research Institute","award":["GYY2023QY01"],"award-info":[{"award-number":["GYY2023QY01"]}]},{"name":"Shandong Province","award":["2022GJJLJRC02-005"],"award-info":[{"award-number":["2022GJJLJRC02-005"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>RNF213 is the first identified susceptibility gene for moyamoya disease, and the encoded protein was recently recognized as a key antimicrobial protein. However, the function of RNF213 in host defense against brain infection remains unclear. Here, we show that increased expression of <jats:italic>Rnf213<\/jats:italic> is significantly regulated by interferon alpha\/beta receptor (IFNAR) signaling during bacterial infection and ligand stimulation. RNF213 deficiency impairs type I interferon (IFN-I) production and decreases the expression of interferon-stimulated genes (ISGs) in response to IFN-\u03b2 stimulation and <jats:italic>Acinetobacter baumannii<\/jats:italic> infection. Mechanistically, RNF213 interacts with TRAF3 and mediates the K27-linked polyubiquitination of TRAF3 at K160. RNF213 regulates the expression of the endothelial tight junction-related genes <jats:italic>Claudin-5, Occludin, and Pecam1<\/jats:italic> via IFN-I signaling. Furthermore, RNF213 deficiency in nonimmune cells increases blood\u2012brain barrier (BBB) disruption and the bacterial load in the brain parenchyma in response to <jats:italic>A. baumannii<\/jats:italic> infection due to impaired IFN-I signaling. Thus, RNF213 mediates BBB integrity by targeting TRAF3 for the regulation of IFN-I signaling against bacterial brain infection. Our study principally provides a deeper understanding of the function of RNF213 and reveals potential therapeutic targets against bacterial brain infection and moyamoya disease.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013333","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T14:19:21Z","timestamp":1751897961000},"page":"e1013333","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["RNF213 regulates blood\u2012brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection"],"prefix":"10.1371","volume":"21","author":[{"given":"Yanfeng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjiang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7982-7486","authenticated-orcid":true,"given":"Xiaopeng","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"issue":"1","key":"ppat.1013333.ref001","doi-asserted-by":"crossref","first-page":"5536","DOI":"10.1038\/s41467-020-19318-3","article-title":"RNF115 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