Toll-like receptors and type 1 diabetes.
Type 1 diabetes (T1D) is an autoimmune disease that results in the progressive loss of insulin producing cells. Studies performed in humans with T1D and animal models of the disease over the past two decades have suggested a key role for the adaptive immune system in disease mechanisms. The role of the innate immune system in triggering T1D was shown only recently. Research in this area was greatly facilitated by the discovery of toll-like receptors (TLRs) that were found to be a key component of the innate immune system that detect microbial infections and initiate antimicrobial host defense responses. New data indicate that in some situations, the innate immune system is associated with mechanisms triggering autoimmune diabetes. In fact, studies preformed in the BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rat models of T1D demonstrate that virus infection leads to islet destruction via mechanisms that may involve TLR9-induced innate immune system activation. Data from these studies also show that TLR upregulation can synergize with virus infection to dramatically increase disease penetrance. Reports from murine models of T1D implicate both MyD88-dependent and MyD88-independent pathways in the course of disease. The new knowledge about the role of innate immune pathways in triggering islet destruction could lead to the discovery of new molecules that may be targeted for disease prevention.
Zipris
Danny
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Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO 80045, USA. danny.zipris@ucdenver.edu
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008954:Models, Biological; D053594:Myeloid Differentiation Factor 88 / Q000737:chemistry; D051381:Rats; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
D053594:Myeloid Differentiation Factor 88; C489640:Tlr9 protein, rat; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors