5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination
Introduction: Excessive immune activation induces tissue damage during infection. Compared to external strategies to reconstruct immune homeostasis, host balancing ways remain largely unclear. Objectives: Here we found a neuroimmune way that prevents infection-induced tissue damage. Methods: By FACS...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000791 |
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| author | Zhenfang Gao Yang Gao Yuxiang Li Jie Zhou Ge Li Shun Xie Ruiyan Jia Lanying Wang Ziying Jiang Meng Liang Chunxiao Du Yaqiong Chen Yinji Liu Lin Du Cong Wang Shuaijie Dou Zhonglin Lv Lubin Wang Renxi Wang Beifen Shen Zhiding Wang Yunfeng Li Gencheng Han |
| author_facet | Zhenfang Gao Yang Gao Yuxiang Li Jie Zhou Ge Li Shun Xie Ruiyan Jia Lanying Wang Ziying Jiang Meng Liang Chunxiao Du Yaqiong Chen Yinji Liu Lin Du Cong Wang Shuaijie Dou Zhonglin Lv Lubin Wang Renxi Wang Beifen Shen Zhiding Wang Yunfeng Li Gencheng Han |
| author_sort | Zhenfang Gao |
| collection | DOAJ |
| description | Introduction: Excessive immune activation induces tissue damage during infection. Compared to external strategies to reconstruct immune homeostasis, host balancing ways remain largely unclear. Objectives: Here we found a neuroimmune way that prevents infection-induced tissue damage. Methods: By FACS and histopathology analysis of brain Streptococcus pneumonia meningitis infection model and behavioral testing. Western blot, co-immunoprecipitation, and ubiquitination analyze the Fluoxetine initiate 5-HT7R-STUB1-CCR5 K48-linked ubiquitination degradation. Results: Fluoxetine, a selective serotonin reuptake inhibitor, or the agonist of serotonin receptor 5-HT7R, protects mice from meningitis by inhibiting CCR5-mediated excessive immune response and tissue damage. Mechanistically, the Fluoxetine-5-HT7R axis induces proteasome-dependent degradation of CCR5 via mTOR signaling, and then recruits STUB1, an E3 ubiquitin ligase, to initiate K48-linked polyubiquitination of CCR5 at K138 and K322, promotes its proteasomal degradation. STUB1 deficiency blocks 5-HT7R-mediated CCR5 degradation. Conclusion: Our results reveal a neuroimmune pathway that balances anti-infection immunity via happiness neurotransmitter receptor and suggest the 5-HT7R-CCR5 axis as a potential target to promote neuroimmune resilience. |
| format | Article |
| id | doaj-art-84d10768f14e40be801bb104d236862b |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-84d10768f14e40be801bb104d236862b2025-01-18T05:04:20ZengElsevierJournal of Advanced Research2090-12322025-02-01683173305-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitinationZhenfang Gao0Yang Gao1Yuxiang Li2Jie Zhou3Ge Li4Shun Xie5Ruiyan Jia6Lanying Wang7Ziying Jiang8Meng Liang9Chunxiao Du10Yaqiong Chen11Yinji Liu12Lin Du13Cong Wang14Shuaijie Dou15Zhonglin Lv16Lubin Wang17Renxi Wang18Beifen Shen19Zhiding Wang20Yunfeng Li21Gencheng Han22Beijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, ChinaBeijing Institute of Basic Medical Sciences, Beijing 100850, China; Corresponding authors.Beijing Institute of Basic Medical Sciences, Beijing 100850, China; Corresponding authors.Beijing Institute of Basic Medical Sciences, Beijing 100850, China; Corresponding authors.Introduction: Excessive immune activation induces tissue damage during infection. Compared to external strategies to reconstruct immune homeostasis, host balancing ways remain largely unclear. Objectives: Here we found a neuroimmune way that prevents infection-induced tissue damage. Methods: By FACS and histopathology analysis of brain Streptococcus pneumonia meningitis infection model and behavioral testing. Western blot, co-immunoprecipitation, and ubiquitination analyze the Fluoxetine initiate 5-HT7R-STUB1-CCR5 K48-linked ubiquitination degradation. Results: Fluoxetine, a selective serotonin reuptake inhibitor, or the agonist of serotonin receptor 5-HT7R, protects mice from meningitis by inhibiting CCR5-mediated excessive immune response and tissue damage. Mechanistically, the Fluoxetine-5-HT7R axis induces proteasome-dependent degradation of CCR5 via mTOR signaling, and then recruits STUB1, an E3 ubiquitin ligase, to initiate K48-linked polyubiquitination of CCR5 at K138 and K322, promotes its proteasomal degradation. STUB1 deficiency blocks 5-HT7R-mediated CCR5 degradation. Conclusion: Our results reveal a neuroimmune pathway that balances anti-infection immunity via happiness neurotransmitter receptor and suggest the 5-HT7R-CCR5 axis as a potential target to promote neuroimmune resilience.http://www.sciencedirect.com/science/article/pii/S20901232240007915-HT7RMeningitisNeuroimmuneUbiquitinationCCR5STUB1 |
| spellingShingle | Zhenfang Gao Yang Gao Yuxiang Li Jie Zhou Ge Li Shun Xie Ruiyan Jia Lanying Wang Ziying Jiang Meng Liang Chunxiao Du Yaqiong Chen Yinji Liu Lin Du Cong Wang Shuaijie Dou Zhonglin Lv Lubin Wang Renxi Wang Beifen Shen Zhiding Wang Yunfeng Li Gencheng Han 5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination Journal of Advanced Research 5-HT7R Meningitis Neuroimmune Ubiquitination CCR5 STUB1 |
| title | 5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination |
| title_full | 5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination |
| title_fullStr | 5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination |
| title_full_unstemmed | 5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination |
| title_short | 5-HT7R enhances neuroimmune resilience and alleviates meningitis by promoting CCR5 ubiquitination |
| title_sort | 5 ht7r enhances neuroimmune resilience and alleviates meningitis by promoting ccr5 ubiquitination |
| topic | 5-HT7R Meningitis Neuroimmune Ubiquitination CCR5 STUB1 |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000791 |
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