The TIM family of cosignaling receptors: emerging targets for the regulation of autoimmune disease and transplantation tolerance.
Currently, lifelong immune suppression regimens are required for solid organ and cellular transplantation and carry significant increased risk of infection, malignancy, and toxicity. For non-life-saving procedures such as islet transplantation, the risk/benefit ratio of lifelong immunosuppression versus benefit from transplantation requires even more careful balance. The search for specific agents to modulate the immune system without chronic immunosuppression is important for the broad application of islet transplantation. The T-cell immunoglobulin mucin (TIM) family is a distinct group of coreceptors that are differentially expressed on T(H)1 and T(H)2 cells, and have the potential to regulate both cytotoxic and humoral immune responses. Completed murine studies demonstrate Tim pathways may be important in the regulation of tolerance to self (auto), harmless (allergic), and transplant (allo) antigen; however, the potential impact of targeting Tim coreceptors has yet to be fully explored in transplantation tolerance induction or autoimmune disease. The current review examines the impact of Tim coreceptor targeting as an emerging therapeutic option for regulating autoimmune diseases and prevention of allograft rejection.
Truong
Wayne
W
The Surgical Medical Research Institute, Department of Surgery, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Shapiro
A M James
AM
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007165:Immunosuppression Therapy; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D009077:Mucins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D009077:Mucins; D011956:Receptors, Cell Surface