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Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes.
Li, Zeying; Zhao, Mingjiu; Li, Jingyue; Luo, Wenjun; Huang, Juan; Huang, Gan; Xie, Zhiguo; Xiao, Yang; Huang, Jiaqi; Li, Xia; Zhao, Bin; Zhou, Zhiguang.
Afiliação
  • Li Z; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Zhao M; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Li J; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Luo W; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Huang J; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China; Section of Endocrinology, Department of Internal Medicine, Sch
  • Huang G; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Xie Z; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Xiao Y; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Huang J; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Li X; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
  • Zhao B; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China; Furong Laboratory, Central South University, Changsha, China.
  • Zhou Z; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China. Electronic address: zhouzhiguang@csu.edu.cn.
Clin Immunol ; 255: 109729, 2023 10.
Article em En | MEDLINE | ID: mdl-37562723
Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune system's failure to maintain self-tolerance, resulting in the autoimmune destruction of pancreatic beta cells. Although T1D has conventionally been viewed as a T-cell-dominant disease, recent research has emphasized the contribution of B cells in the onset of the disease. However, the mechanism underlying aberrant B cell responses remains unknown. B cell metabolism is a crucial prerequisite for B cell function and the development of adaptive immune responses. Here, we investigated the metabolic features of B cells, first in a cross-sectional cohort and subsequently in non-obese diabetic (NOD) mice, and revealed that there is an increased frequency of high-glucose-avidity (2-NBDGhigh) B cell population that may contribute to T1D progression. Further characterization of the metabolic, transcriptional and functional phenotype of B cells in NOD mice found that elevated glucose avidity is associated with a greater capacity for co-stimulation, proliferation and inflammatory cytokine production. Mechanistically, elevated Myc signaling orchestrated the glucose metabolism and the pro-inflammatory response of B cells in T1D. In vitro experiments demonstrated that pharmacological inhibition of glucose metabolism using metformin and 2-DG reduced pro-inflammatory cytokine production and B cell proliferation. Moreover, the combination of these inhibitors successfully delayed insulitis development, onset of diabetes, and improved high blood glucose levels in streptozotocin (STZ)-induced diabetic mice model. Taken together, our work has uncovered these high-glucose-avidity B cells as novel adjuvant diagnostic and therapeutic targets for T1D.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 Tipo de estudo: Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Clin Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 Tipo de estudo: Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Clin Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China
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