New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes
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 i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.914136/full |
| _version_ | 1828335387217494016 |
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| author | Mengdi Zhang Yanyan Zhou Zhiguo Xie Shuoming Luo Zhiguang Zhou Jiaqi Huang Bin Zhao |
| author_facet | Mengdi Zhang Yanyan Zhou Zhiguo Xie Shuoming Luo Zhiguang Zhou Jiaqi Huang Bin Zhao |
| author_sort | Mengdi Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T21:46:39Z |
| format | Article |
| id | doaj.art-cd58825160234d6fa633cbb6faf9ff38 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T21:46:39Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-cd58825160234d6fa633cbb6faf9ff382022-12-22T02:28:34ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.914136914136New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 DiabetesMengdi Zhang0Yanyan Zhou1Zhiguo Xie2Shuoming Luo3Zhiguang Zhou4Jiaqi Huang5Bin Zhao6National 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, ChinaDepartment of Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaType 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.914136/fulltype 1 diabetesT cellT cell differentiation and functionT cell metabolismautoimmunity |
| spellingShingle | Mengdi Zhang Yanyan Zhou Zhiguo Xie Shuoming Luo Zhiguang Zhou Jiaqi Huang Bin Zhao New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes Frontiers in Endocrinology type 1 diabetes T cell T cell differentiation and function T cell metabolism autoimmunity |
| title | New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes |
| title_full | New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes |
| title_fullStr | New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes |
| title_full_unstemmed | New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes |
| title_short | New Developments in T Cell Immunometabolism and Therapeutic Implications for Type 1 Diabetes |
| title_sort | new developments in t cell immunometabolism and therapeutic implications for type 1 diabetes |
| topic | type 1 diabetes T cell T cell differentiation and function T cell metabolism autoimmunity |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.914136/full |
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