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(T...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.展开更多
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)+2 种基金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).
文摘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.
