دورية أكاديمية
2-Bromo-1,4-Naphthalenedione promotes CD8 + T cell expansion and limits Th1/Th17 to mitigate experimental autoimmune encephalomyelitis.
| العنوان: | 2-Bromo-1,4-Naphthalenedione promotes CD8 + T cell expansion and limits Th1/Th17 to mitigate experimental autoimmune encephalomyelitis. |
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| المؤلفون: | Yang C; Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, China.; Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, China., Ma Y; Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Lu Q; Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, China., Qu Y; Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, China., Li Y; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-Sen University, Ministry of Education, Guangzhou, China., Cheng S; Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, China., Xiao C; Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, China., Chen J; Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, China., Wang C; Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, China., Wang F; Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Xiang AP; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-Sen University, Ministry of Education, Guangzhou, China.; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China., Huang W; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-Sen University, Ministry of Education, Guangzhou, China. hweijun@mail.sysu.edu.cn., Tang X; Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, China. 372730132@qq.com., Zheng H; Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, China. zhenghq2@mail.sysu.edu.cn. |
| المصدر: | Journal of neuroinflammation [J Neuroinflammation] 2024 Jul 27; Vol. 21 (1), pp. 181. Date of Electronic Publication: 2024 Jul 27. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : BioMed Central, c2004- |
| مواضيع طبية MeSH: | Encephalomyelitis, Autoimmune, Experimental*/immunology , Encephalomyelitis, Autoimmune, Experimental*/drug therapy , Encephalomyelitis, Autoimmune, Experimental*/pathology , CD8-Positive T-Lymphocytes*/drug effects , CD8-Positive T-Lymphocytes*/immunology , Th1 Cells*/drug effects , Th1 Cells*/immunology , Th17 Cells*/drug effects , Th17 Cells*/immunology , Mice, Inbred C57BL*, Animals ; Mice ; Female ; Naphthalenes/pharmacology ; Naphthalenes/therapeutic use ; Cell Proliferation/drug effects |
| مستخلص: | Treating Multiple sclerosis (MS), a well-known immune-mediated disease characterized by axonal demyelination, is challenging due to its complex causes. Naphthalenedione, present in numerous plants, is being explored as a potential medicine for MS due to its immunomodulatory properties. However, its effects on lymphocytes can vary depending on factors such as the specific compound, concentration, and experimental conditions. In this study, we aim to explore the therapeutic potential of 2-bromo-1,4-naphthalenedione (BrQ), a derivative of naphthalenedione, in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and to elucidate its underlying mechanisms. We observed that mice treated with BrQ exhibited reduced severity of EAE symptoms, including lower clinical scores, decreased leukocyte infiltration, and less extensive demyelination in central nervous system. Furthermore, it was noted that BrQ does not directly affect the remyelination process. Through cell-chat analysis based on bulk RNA-seq data, coupled with validation of flow analysis, we discovered that BrQ significantly promotes the expansion of CD8 + T cells and their interactions with other immune cells in peripheral immune system in EAE mice. Subsequent CD8 + T cell depletion experiments confirmed that BrQ alleviates EAE in a CD8 + T cell-dependent manner. Mechanistically, expanded CD8 + cells were found to selectively reduce antigen-specific CD4 + cells and subsequently inhibit Th1 and Th17 cell development in vivo, ultimately leading to relief from EAE. In summary, our findings highlight the crucial role of BrQ in modulating the pathogenesis of MS, suggesting its potential as a novel drug candidate for treating MS and other autoimmune diseases. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | 82101879 National Natural Science Foundation of China; 82272605 National Natural Science Foundation of China; 2020M671146 China Postdoctoral Science Foundation |
| فهرسة مساهمة: | Keywords: 2-bromo-1,4-Naphthalenedione; CD8+ T cells; Experimental autoimmune encephalomyelitis; Th1; Th17 |
| المشرفين على المادة: | 0 (Naphthalenes) |
| تواريخ الأحداث: | Date Created: 20240727 Date Completed: 20240728 Latest Revision: 20240730 |
| رمز التحديث: | 20240730 |
| مُعرف محوري في PubMed: | PMC11283727 |
| DOI: | 10.1186/s12974-024-03172-x |
| PMID: | 39068463 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1742-2094 |
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| DOI: | 10.1186/s12974-024-03172-x |