Induced regulatory T cells suppress Tel cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus  

作　　者：Li Zhou Xuemin He Peihong Cai Ting Li Rongdong Peng Junlong Dang Yue Li Haicheng Li Feng Huang Guojun Shi Chichu Xie Yan Lu Yanming Chen 

机构地区：[1]Department of Endocrinology and Metabolism,Guangdong Provincial Key Laboratory of Diabetology,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630 Guangdong,China [2]Department of Clinical Immunology,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630 Guangdong,China

出　　处：《Cellular & Molecular Immunology》2021年第3期698-710,共13页中国免疫学杂志（英文版）

基　　金：supported by the National Key R&D Program of China(2017YFAO105803);the general program of the National Natural Science Foundation of China(81770826);the Science and Technology Plan Projects of Guangdong Province(2019B020227003);the Key Special Projects of Medical and Health of Guangzhou City(202007040003);the 5010 Clinical Research Projects of Sun Yatsen University(2015015).

摘　　要：Type 1 diabetes mellitus(T1D)is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic β cells.In addition to well-established pathogenic effector T cells,regulatory T cells(Tregs)have also been shown to be defective in T1D.Thus,an increasing number of therapeutic approaches are being developed to target Tregs.However,the role and mechanisms of TGF-β-induced Tregs(iTregs)in T1D remain poorly understood.Here,using a streptozotocin(STZ)-induced preclinical T1D mouse model,we found that iTregs could ameliorate the development of T1D and preserve β cell function.The preventive effect was associated with the inhibition of type 1 cytotoxic T(Tel)cell function and rebalancing the Treg/Tc1 cell ratio in recipients.Furthermore,we showed that the underlying mechanisms were due to the TGF-β-mediated combinatorial actions of mTOR and TCF1.In addition to the preventive role,the therapeutic effects of iTregs on the established STZ-T1D and nonobese diabetic(NOD)mouse models were tested,which revealed improved β cell function.Our findings therefore provide key new insights into the basic mechanisms involved in the therapeutic role of iTregs in T1D.

关 键 词：type 1 diabetes mellitus induced regulatory T cells type 1 cytotoxic T cells TGF-Β mTOR and TCF1 

分 类 号：R587.1[医药卫生—内分泌]