2. Academic Validation
  3. RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection

RNF213 regulates blood‒brain barrier integrity by targeting TRAF3 for type I interferon activation during A. baumannii infection

  • PLoS Pathog. 2025 Jul 7;21(7):e1013333. doi: 10.1371/journal.ppat.1013333.
Yanfeng Li 1,  Qingqing Xie 1,  Luyu Yang 1,  Qian Jiang 2 3,  Zhiping Liu 2,  Chengjiang Gao 4 5,  Xiaopeng Qi 1 6,  Tao Xu 1
Affiliations

Affiliations

  • 1 Key Laboratory for Experimental Teratology of the Ministry of Education, Advanced Medical Research Institute, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2 School of Nursing; Gannan Medical UniversityGanzhou, Jiangxi, China.
  • 3 School of Graduate, China Medical University, Shenyang, Liaoning, China.
  • 4 Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province & Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, China.
  • 5 Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, China.
  • 6 State Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, China.
PMID: 40623121 DOI: 10.1371/journal.ppat.1013333
Abstract

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.

Figures
Products