Since their discovery two decades ago,CD4+CD25+Foxp3+ regulatory T cells(Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells,which promote an immune response,Tregs actively i...Since their discovery two decades ago,CD4+CD25+Foxp3+ regulatory T cells(Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells,which promote an immune response,Tregs actively inhibit inflammation when activated by their cognate antigen,thus raising hope that these cells could be engineered into a highly targeted,antigenspecific,immunosuppressant therapy. Although Tregs represent less than 10% of circulating CD4+T cells,they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular,spontaneous intestinal inflammation has been shown to occur in the absence of Tregs,suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease(IBD). However,over the past decade,multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBD patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review,we will discuss the history of Tregs,what is known about them in IBD,and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit.展开更多
Foxp3^(+)T regulatory cells(Tregs)consisting of natural and induced Treg subsets play a crucial role in the maintenance of immune homeostasis against self-antigen.The actions designed to correct defects in numbers or ...Foxp3^(+)T regulatory cells(Tregs)consisting of natural and induced Treg subsets play a crucial role in the maintenance of immune homeostasis against self-antigen.The actions designed to correct defects in numbers or functions of Tregs may be therapeutic in the treatment of autoimmune diseases.While recent studies demonstrated that natural Tregs are instable and dysfunctional in the in-flammatory condition,induced Tregs(iTregs)may have a different feature.Here we review the progress of iTregs,particularly focus on their stability and function in the established autoimmune diseases.The advantage of iTregs as therapeutics used under inflammatory conditions is highlighted.Proper generation and manipulation of iTregs used for cellular therapy may provide a promise for the treatment of many autoimmune and inflammatory diseases.展开更多
文摘Since their discovery two decades ago,CD4+CD25+Foxp3+ regulatory T cells(Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells,which promote an immune response,Tregs actively inhibit inflammation when activated by their cognate antigen,thus raising hope that these cells could be engineered into a highly targeted,antigenspecific,immunosuppressant therapy. Although Tregs represent less than 10% of circulating CD4+T cells,they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular,spontaneous intestinal inflammation has been shown to occur in the absence of Tregs,suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease(IBD). However,over the past decade,multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBD patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review,we will discuss the history of Tregs,what is known about them in IBD,and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit.
基金supported by the grants from the NIH R01 AR 059103(NIH P30 DK048522)Arthritis Foundation+7 种基金Wright Foundationthe Arthritis National Research Foundationthe Clinical Research Feasibility Fundthe James H.Zumberge Faculty Research and Innovation Fundthe Outstanding Youth Scientist Award from the National Natural Science Foundation of China(30728007)the American College of Rheumatology Research and Education’s Within Our Reach:Finding a Cure for Rheumatoid Arthritis campaign(all to S.G.Z.)Regular Project from National Nature Science Foundation of China(30772150,to H.M.F.)Le Studium and European FEDER grant support(B.R.,V.Q.).
文摘Foxp3^(+)T regulatory cells(Tregs)consisting of natural and induced Treg subsets play a crucial role in the maintenance of immune homeostasis against self-antigen.The actions designed to correct defects in numbers or functions of Tregs may be therapeutic in the treatment of autoimmune diseases.While recent studies demonstrated that natural Tregs are instable and dysfunctional in the in-flammatory condition,induced Tregs(iTregs)may have a different feature.Here we review the progress of iTregs,particularly focus on their stability and function in the established autoimmune diseases.The advantage of iTregs as therapeutics used under inflammatory conditions is highlighted.Proper generation and manipulation of iTregs used for cellular therapy may provide a promise for the treatment of many autoimmune and inflammatory diseases.
