CD40 is required for development of islet inflammation in the RIP-CD154 transgenic mouse model of type 1 diabetes.
Type 1 diabetes is believed to be an autoimmune disease where cells of the immune system destroy the insulin-producing beta cells in the islets of Langerhans. The trigger(s) of the inflammatory reaction is yet unknown, but both genetic and environmental factors, including viruses or other pathogens, are thought to play a role. We have recently described a transgenic mouse model--the RIP-CD154 mouse--in which beta-cell-specific expression of CD154 (CD40 ligand) mediates immune activation, insulitis, and diabetes on a non-diabetes-prone background. By the use of bone marrow chimeric mice, we now demonstrate that a functional Cd40 gene is necessary for islet inflammation and we show that CD40 expression on bone marrow-derived cells is sufficient to trigger activation of the immune system and development of insulitis.
Haase
Claus
C
Hagedorn Research Institute and Novo Nordisk A/S, Department of Immunopharmacology, Novo Nordisk Park, DK-2760 Måløv, Denmark. csha@novonordisk.com
Markholst
Helle
H
D000818:Animals; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010182:Pancreatic Diseases / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D051381:Rats