Genetic manipulation of islet cells in autoimmune diabetes: from bench to bedside.
Type 1 diabetes (T1D) develops via spontaneous autoimmune destruction of pancreatic beta cells. The immunoprogression and effectors of T1D have been determined using non-obese diabetic (NOD) mouse mode. Transgenic mice overexpressing a variety of transgenes driven by insulin promoter demonstrate that both apoptosis and necrosis lead to islet cells death; furthermore, various immune cells and cytokine effectors are involved in the immunoprogression of T1D. Efficiently halting immune attack in the islet milieu by an effector-specific manner apparently provides the preventive and therapeutic strategies in T1D. Islet transplantation has been reported as an appropriate treatment to accomplish insulin independence and long-term homeostasis of glucose in T1D. However, it is difficult to protect the islet grafts from subsequent immune attack and prolong their survival. In this review, we highlight the transgenic mice that express transgenes restricted in islet cells to depict the complicated interactions of immune cells in inflammatory islets, to investigate the protective efficacy of some immunomodulatory genes, and to develop genetically-modified islets tolerant to immune attack that might be used in future clinical application.
Chuang
Yi-Ping
YP
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Chu
Chi-Hong
CH
Sytwu
Huey-Kang
HK
D015703:Antigens, CD / Q000276:immunology; D060908:CTLA-4 Antigen; D016923:Cell Death; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D051547:Heme Oxygenase-1 / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007371:Interferon-gamma / Q000502:physiology; D007515:Islets of Langerhans / Q000503:physiopathology*; D016381:Islets of Langerhans Transplantation; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013879:Thioredoxins / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D013879:Thioredoxins; D007371:Interferon-gamma; D051547:Heme Oxygenase-1