title: Role of TLR2 in the pathogenesis of autoimmune diabetes and its therapeutic implication.
abstract: Recently, a couple of articles suggested the possibility that apoptosis of pancreatic β-cells induces inflammatory/immune responses to β-cells. Such a theory is based on the assumption that apoptotic cells can, under certain circumstances, induce immune responses, inflammatory and autoimmune disorders, which is in contrast to the dogma that apoptotic cells result in immunosuppression and necrotic cells provoke inflammation/immunity. We observed that late apoptotic β-cells with secondary necrosis elicited inflammatory responses in macrophages through the toll-like receptor 2 (TLR2)/MyD88/nuclear factor-κB signalling pathway. Late apoptotic cells also induced TLR2-dependent maturation of dendritic cells and then activation of autoreactive T-cells. TLR2 knockout mice showed defective priming of diabetogenic T-cells by apoptotic β-cells in the pancreatic lymph nodes. Furthermore, TLR2 deficiency conferred a significant protection against type 1 diabetes (T1D) and insulitis in T1D animal models. These findings present evidence suggesting that apoptosis of pancreatic β-cells could be one of the initial events in T1D and provide a novel strategy for therapeutic or preventive intervention in T1D.
authors: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Myung-Shik
authors: MS
authors: Lee
authors: Do-Hoon
authors: DH
authors: Kim
authors: June-Chul
authors: JC
authors: Lee
authors: Sunshin
authors: S
authors: Kim
authors: Hun Sik
authors: HS
authors: Kim
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology; D050417:Insulin-Secreting Cells / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2