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Nevertheless, the underlying mechanisms responsible for barrier impairment remain inadequately understood. Here, by analyzing the protein profiles in peripheral blood serum, chemokine (C\u2010X\u2010C motif) ligand 13 (CXCL13) was identified to be increased with the progression of MS and EAE. The absence of CXCL13 resulted in alleviation of EAE symptoms, as evidenced by a reduced clinical score, decreased barrier damage, as well as diminished demyelination and inflammatory response in the spinal cord. In the BSCB model, CXCL13 was found to impair barrier structure and function in a dose\u2010 and time\u2010dependent manner, which was associated with exacerbated autophagy in endothelial cells, while the application of autophagy inhibitors partially mitigated this damage. Mechanistically, CXCL13 enhanced the expression of RNF6, an E3 ubiquitin\u2010protein ligase, facilitating the conjugation to Sqstm1 for the ubiquitination at the K314 residue. These findings suggest that CXCL13 significantly contributes to the impairment of the BSCB by promoting RNF6\/Sqstm1\u2010ubiquitination\u2010induced autophagy during the progression of EAE, thereby offering a promising diagnostic and therapeutic target for MS.<\/jats:p>","DOI":"10.1002\/advs.202414550","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T08:03:33Z","timestamp":1744704213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6\/Sqstm1\u2010Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis"],"prefix":"10.1002","volume":"12","author":[{"given":"Jingjing","family":"Han","sequence":"first","affiliation":[{"name":"Department of Basic Medical Science Jiangsu Medical College  Yancheng Jiangsu 224005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science Jiangsu Medical College  Yancheng Jiangsu 224005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Cao","sequence":"additional","affiliation":[{"name":"The Fourth People's Hospital of Yancheng  Yancheng Jiangsu 224003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanhua","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology Xuzhou Medical University  Xuzhou Jiangsu 221004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Emergency Medicine Department of the Affiliated Hospital of Xuzhou Medical University  Xuzhou Jiangsu 221000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology Xuzhou Medical University  Xuzhou Jiangsu 221004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science Jiangsu Medical College  Yancheng Jiangsu 224005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Yang","sequence":"additional","affiliation":[{"name":"Group Health Section The Affiliated Yancheng Maternity &amp; Child Health Hospital of Yangzhou University  Yancheng Jiangsu 224000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology Xuzhou Medical University  Xuzhou Jiangsu 221004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Fourth People's Hospital of Yancheng  Yancheng Jiangsu 224003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-5695","authenticated-orcid":false,"given":"Xuebin","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science Jiangsu Medical College  Yancheng Jiangsu 224005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.26858"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202106150"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00289-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00063-6"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-093019-124155"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00377-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac019"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00050.2017"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1207-5"},{"key":"e_1_2_9_8_1","unstructured":"S. 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