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Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes.
Zou, Yuan; Zhang, Jing; Sun, Fei; Xu, Qianqian; Chen, Longmin; Luo, Xi; Wang, Ting; Zhou, Qing; Zhang, Shu; Xiong, Fei; Kong, Wen; Yang, Ping; Yu, Qilin; Liu, Shiwei; Wang, Cong-Yi.
Afiliación
  • Zou Y; The 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 Technology, Wuhan, China.
  • Zhang J; The 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 Technology, Wuhan, China.
  • Sun F; The 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 Technology, Wuhan, China.
  • Xu Q; The 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 Technology, Wuhan, China.
  • Chen L; The 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 Technology, Wuhan, China.
  • Luo X; Department of Rheumatology and Immunology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.
  • Wang T; The 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 Technology, Wuhan, China.
  • Zhou Q; The 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 Technology, Wuhan, China.
  • Zhang S; The 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 Technology, Wuhan, China.
  • Xiong F; The 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 Technology, Wuhan, China.
  • Kong W; The 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 Technology, Wuhan, China.
  • Yang P; Department of Endocrinology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.
  • Yu Q; The 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 Technology, Wuhan, China.
  • Liu S; The 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 Technology, Wuhan, China. qlyu@tjh.tjmu.edu.cn.
  • Wang CY; Department 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 University, Taiyuan, China. lswspring6@aliyun.com.
Mol Med ; 30(1): 23, 2024 Feb 05.
Article en En | MEDLINE | ID: mdl-38317106
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 ß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Diabetes Mellitus Tipo 1 Límite: Animals / Humans Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Diabetes Mellitus Tipo 1 Límite: Animals / Humans Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido