CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis
Abstract The damage of blood spinal cord barrier (BSCB) is contributing to the disruption of immune microenvironment within central nervous system during the progression of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Nevertheless, the underlying mechanisms responsible...
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Wiley
2025-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202414550 |
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| author | Jingjing Han Rui Hong Cong Cao Wanhua Feng Wei Zhuang Gui Wang Jingchao Tang Ya Yang Chu Zhang Aihua Zhou Xuebin Qu |
| author_facet | Jingjing Han Rui Hong Cong Cao Wanhua Feng Wei Zhuang Gui Wang Jingchao Tang Ya Yang Chu Zhang Aihua Zhou Xuebin Qu |
| author_sort | Jingjing Han |
| collection | DOAJ |
| description | Abstract The damage of blood spinal cord barrier (BSCB) is contributing to the disruption of immune microenvironment within central nervous system during the progression of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Nevertheless, the underlying mechanisms responsible for barrier impairment remain inadequately understood. Here, by analyzing the protein profiles in peripheral blood serum, chemokine (C‐X‐C 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‐ and time‐dependent 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‐protein 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‐ubiquitination‐induced autophagy during the progression of EAE, thereby offering a promising diagnostic and therapeutic target for MS. |
| format | Article |
| id | doaj-art-19b9a922cec748fc849fbe70e423a63a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-19b9a922cec748fc849fbe70e423a63a2025-08-20T03:26:10ZengWileyAdvanced Science2198-38442025-06-011221n/an/a10.1002/advs.202414550CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic EncephalomyelitisJingjing Han0Rui Hong1Cong Cao2Wanhua Feng3Wei Zhuang4Gui Wang5Jingchao Tang6Ya Yang7Chu Zhang8Aihua Zhou9Xuebin Qu10Department of Basic Medical Science Jiangsu Medical College Yancheng Jiangsu 224005 ChinaDepartment of Basic Medical Science Jiangsu Medical College Yancheng Jiangsu 224005 ChinaThe Fourth People's Hospital of Yancheng Yancheng Jiangsu 224003 ChinaDepartment of Cell Biology and Neurobiology Xuzhou Medical University Xuzhou Jiangsu 221004 ChinaEmergency Medicine Department of the Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu 221000 ChinaDepartment of Cell Biology and Neurobiology Xuzhou Medical University Xuzhou Jiangsu 221004 ChinaDepartment of Basic Medical Science Jiangsu Medical College Yancheng Jiangsu 224005 ChinaGroup Health Section The Affiliated Yancheng Maternity & Child Health Hospital of Yangzhou University Yancheng Jiangsu 224000 ChinaDepartment of Cell Biology and Neurobiology Xuzhou Medical University Xuzhou Jiangsu 221004 ChinaThe Fourth People's Hospital of Yancheng Yancheng Jiangsu 224003 ChinaDepartment of Basic Medical Science Jiangsu Medical College Yancheng Jiangsu 224005 ChinaAbstract The damage of blood spinal cord barrier (BSCB) is contributing to the disruption of immune microenvironment within central nervous system during the progression of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Nevertheless, the underlying mechanisms responsible for barrier impairment remain inadequately understood. Here, by analyzing the protein profiles in peripheral blood serum, chemokine (C‐X‐C 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‐ and time‐dependent 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‐protein 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‐ubiquitination‐induced autophagy during the progression of EAE, thereby offering a promising diagnostic and therapeutic target for MS.https://doi.org/10.1002/advs.202414550autophagyblood spinal cord barriersCXCL13experimental allergic encephalomyelitismultiple sclerosisRNF6 |
| spellingShingle | Jingjing Han Rui Hong Cong Cao Wanhua Feng Wei Zhuang Gui Wang Jingchao Tang Ya Yang Chu Zhang Aihua Zhou Xuebin Qu CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis Advanced Science autophagy blood spinal cord barriers CXCL13 experimental allergic encephalomyelitis multiple sclerosis RNF6 |
| title | CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis |
| title_full | CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis |
| title_fullStr | CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis |
| title_full_unstemmed | CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis |
| title_short | CXCL13 Damages Blood Spinal Cord Barrier by Promoting RNF6/Sqstm1‐Ubiquitination Induced Autophagy in Experimental Allergic Encephalomyelitis |
| title_sort | cxcl13 damages blood spinal cord barrier by promoting rnf6 sqstm1 ubiquitination induced autophagy in experimental allergic encephalomyelitis |
| topic | autophagy blood spinal cord barriers CXCL13 experimental allergic encephalomyelitis multiple sclerosis RNF6 |
| url | https://doi.org/10.1002/advs.202414550 |
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