Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes
Abstract Background Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-024-00791-1 |
| _version_ | 1797274216406450176 |
|---|---|
| author | Yuan Zou Jing Zhang Fei Sun Qianqian Xu Longmin Chen Xi Luo Ting Wang Qing Zhou Shu Zhang Fei Xiong Wen Kong Ping Yang Qilin Yu Shiwei Liu Cong-Yi Wang |
| author_facet | Yuan Zou Jing Zhang Fei Sun Qianqian Xu Longmin Chen Xi Luo Ting Wang Qing Zhou Shu Zhang Fei Xiong Wen Kong Ping Yang Qilin Yu Shiwei Liu Cong-Yi Wang |
| author_sort | Yuan Zou |
| collection | DOAJ |
| description | Abstract Background Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. Method Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. Result Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. Conclusion Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting. |
| first_indexed | 2024-03-07T14:56:09Z |
| format | Article |
| id | doaj.art-238391e691734f4d9e4df48956728c78 |
| institution | Directory Open Access Journal |
| issn | 1528-3658 |
| language | English |
| last_indexed | 2024-03-07T14:56:09Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-238391e691734f4d9e4df48956728c782024-03-05T19:25:39ZengBMCMolecular Medicine1528-36582024-02-0130111510.1186/s10020-024-00791-1Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetesYuan Zou0Jing Zhang1Fei Sun2Qianqian Xu3Longmin Chen4Xi Luo5Ting Wang6Qing Zhou7Shu Zhang8Fei Xiong9Wen Kong10Ping Yang11Qilin Yu12Shiwei Liu13Cong-Yi Wang14The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyDepartment of Endocrinology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyDepartment of Endocrinology, Shanxi Bethune Hospital, Shanxi Academy of Medical ScienceTongji Shanxi Hospital, The Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province, Third Hospital of Shanxi Medical UniversityThe Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory for Respiratory Diseases, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and TechnologyAbstract Background Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. Method Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. Result Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. Conclusion Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting.https://doi.org/10.1186/s10020-024-00791-1Type 1 diabetesFluvoxamineTh1 and Th17 differentiationGlycolysisPI3K-AKT signaling |
| spellingShingle | Yuan Zou Jing Zhang Fei Sun Qianqian Xu Longmin Chen Xi Luo Ting Wang Qing Zhou Shu Zhang Fei Xiong Wen Kong Ping Yang Qilin Yu Shiwei Liu Cong-Yi Wang Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes Molecular Medicine Type 1 diabetes Fluvoxamine Th1 and Th17 differentiation Glycolysis PI3K-AKT signaling |
| title | Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes |
| title_full | Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes |
| title_fullStr | Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes |
| title_full_unstemmed | Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes |
| title_short | Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes |
| title_sort | fluvoxamine inhibits th1 and th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes |
| topic | Type 1 diabetes Fluvoxamine Th1 and Th17 differentiation Glycolysis PI3K-AKT signaling |
| url | https://doi.org/10.1186/s10020-024-00791-1 |
| work_keys_str_mv | AT yuanzou fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT jingzhang fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT feisun fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT qianqianxu fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT longminchen fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT xiluo fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT tingwang fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT qingzhou fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT shuzhang fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT feixiong fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT wenkong fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT pingyang fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT qilinyu fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT shiweiliu fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes AT congyiwang fluvoxamineinhibitsth1andth17polarizationandfunctionbyrepressingglycolysistoattenuateautoimmuneprogressionintype1diabetes |