RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection.
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 Rnf213 is signi...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013333 |
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| author | Yanfeng Li Qingqing Xie Luyu Yang Qian Jiang Zhiping Liu Chengjiang Gao Xiaopeng Qi Tao Xu |
| author_facet | Yanfeng Li Qingqing Xie Luyu Yang Qian Jiang Zhiping Liu Chengjiang Gao Xiaopeng Qi Tao Xu |
| author_sort | Yanfeng Li |
| collection | DOAJ |
| description | 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 Rnf213 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-β stimulation and Acinetobacter baumannii 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 Claudin-5, Occludin, and Pecam1 via IFN-I signaling. Furthermore, RNF213 deficiency in nonimmune cells increases blood‒brain barrier (BBB) disruption and the bacterial load in the brain parenchyma in response to A. baumannii 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. |
| format | Article |
| id | doaj-art-5c77fda84b5f428e8c7d04cb2709c77a |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-5c77fda84b5f428e8c7d04cb2709c77a2025-08-20T02:40:30ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-07-01217e101333310.1371/journal.ppat.1013333RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection.Yanfeng LiQingqing XieLuyu YangQian JiangZhiping LiuChengjiang GaoXiaopeng QiTao XuRNF213 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 Rnf213 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-β stimulation and Acinetobacter baumannii 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 Claudin-5, Occludin, and Pecam1 via IFN-I signaling. Furthermore, RNF213 deficiency in nonimmune cells increases blood‒brain barrier (BBB) disruption and the bacterial load in the brain parenchyma in response to A. baumannii 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.https://doi.org/10.1371/journal.ppat.1013333 |
| spellingShingle | Yanfeng Li Qingqing Xie Luyu Yang Qian Jiang Zhiping Liu Chengjiang Gao Xiaopeng Qi Tao Xu RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection. PLoS Pathogens |
| title | RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection. |
| title_full | RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection. |
| title_fullStr | RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection. |
| title_full_unstemmed | RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection. |
| title_short | RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection. |
| title_sort | rnf213 regulates blood brain barrier integrity by targeting traf3 for type i interferon activation during a baumannii infection |
| url | https://doi.org/10.1371/journal.ppat.1013333 |
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