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New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes.

Authors:
Mengdi Zhang Yanyan Zhou Zhiguo Xie Shuoming Luo Zhiguang Zhou Jiaqi Huang Bin Zhao

Front Endocrinol (Lausanne) 2022 10;13:914136. Epub 2022 Jun 10.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Type 1 diabetes (T1D) is an autoimmune disease mediated by T cells and is becoming a serious public health threat. Despite the increasing incidence rate of T1D worldwide, our understanding of why T1D develops and how T cells lose their self-tolerance in this process remain limited. Recent advances in immunometabolism have shown that cellular metabolism plays a fundamental role in shaping T cell responses. T cell activation and proliferation are supported by metabolic reprogramming to meet the increased energy and biomass demand, and deregulation in immune metabolism can lead to autoimmune disorders. Specific metabolic pathways and factors have been investigated to rectify known deficiencies in several autoimmune diseases, including T1D. Most therapeutic strategies have concentrated on aerobic glycolysis to limit T cell responses, whereas glycolysis is the main metabolic pathway for T cell activation and proliferation. The use of metabolic inhibitors, especially glycolysis inhibitors may largely leave T cell function intact but primarily target those autoreactive T cells with hyperactivated metabolism. In this review, we provide an overview of metabolic reprogramming used by T cells, summarize the recent findings of key metabolic pathways and regulators modulating T cell homeostasis, differentiation, and function in the context of T1D, and discuss the opportunities for metabolic intervention to be employed to suppress autoreactive T cells and limit the progression of β-cell destruction.

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http://dx.doi.org/10.3389/fendo.2022.914136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226440PMC
June 2022

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