Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in nonobese diabetic mice.
Decoy receptor 3 (DCR3) halts both Fas ligand- and LIGHT-induced cell deaths, which are required for pancreatic beta cell damage in autoimmune diabetes. To directly investigate the therapeutic potential of DCR3 in preventing this disease, we generated transgenic nonobese diabetic mice, which overexpressed DCR3 in beta cells. Transgenic DCR3 protected mice from autoimmune and cyclophosphamide-induced diabetes in a dose-dependent manner and significantly reduced the severity of insulitis. Local expression of the transgene did not alter the diabetogenic properties of systemic lymphocytes or the development of T helper 1 or T regulatory cells. The transgenic islets had a higher transplantation success rate and survived for longer than wild-type islets. We have demonstrated for the first time that the immune-evasion function of DCR3 inhibits autoimmunity and that genetic manipulation of grafts may improve the success and survival of islet transplants.
Sung
Hsiang-Hsuan
HH
Graduate Institute of Life Sciences, National Defense Medical Center, MinChuan East Road, Neihu, Taipei, Taiwan.
Juang
Jyuhn-Huarng
JH
Lin
Yu-Chun
YC
Kuo
Chien-Hung
CH
Hung
Jung-Tung
JT
Chen
An
A
Chang
Der-Ming
DM
Chang
Sun-Yran
SY
Hsieh
Shie-Liang
SL
Sytwu
Huey-Kang
HK
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D015870:Gene Expression; D006085:Graft Survival; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D017931:DNA Primers; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b