TGF-β-mediated crosstalk between TIGIT + Tregs and CD226 + CD8 + T cells in the progression and remission of type 1 diabetes.

Autor: Zhong T; 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, Hunan, China., Li X; 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, Hunan, China., Lei K; 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, Hunan, China., Tang R; 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, Hunan, China., Deng Q; Department of Physiology and Pharmacology, Karolinska Institute, 17177, Solna, Sweden., Love PE; Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Zhou Z; 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, Hunan, China. zhouzhiguang@csu.edu.cn., Zhao B; 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, Hunan, China. binzhao@csu.edu.cn.; CSU-Sinocare Research Center for Nutrition and Metabolic Health, Xiangya School of Public Health, Central South University, Changsha, Hunan, China. binzhao@csu.edu.cn.; Furong Laboratory, Changsha, Hunan, China. binzhao@csu.edu.cn., Li X; 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, Hunan, China. lixia@csu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 15; Vol. 15 (1), pp. 8894. Date of Electronic Publication: 2024 Oct 15.
DOI: 10.1038/s41467-024-53264-8
Abstrakt: Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by hyperglycemia resulting from the destruction of insulin-producing β-cells that is traditionally deemed irreversible, but partial remission (PR) with temporary reversal of hyperglycemia is sometimes observed. Here we use single-cell RNA sequencing to delineate the immune cell landscape across patients in different T1D stages. Together with cohort validation and functional assays, we observe dynamic changes in TIGIT + CCR7 - Tregs and CD226 + CCR7 - CD8 + cytotoxic T cells during the peri-remission phase. Machine learning algorithms further identify TIGIT + CCR7 - Tregs and CD226 + CD8 + T cells as biomarkers for β-cell function decline in a predictive model, while cell communication analysis and in vitro assays suggest that TIGIT + CCR7 - Tregs may inhibit CD226 + CCR7 - CD8 + T cells via TGF-β signaling. Lastly, in both cyclophosphamide-induced and streptozotocin (STZ)-induced mouse diabetes models, CD226 inhibition postpones insulitis onset and reduces hyperglycemia severity. Our results thus identify two interrelated immune cell subsets that may serve as biomarkers for monitoring disease progression and targets for therapeutic intervention of T1D.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: