title: Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes.
abstract: Although it is established that defective clearance and, hence, increased accumulation of apoptotic cells can lead to autoimmunity, the mechanism by which this occurs remains elusive. Here, we observed that apoptotic cells undergoing secondary necrosis but not intact apoptotic cells provoked substantial immune responses, which were mediated through the toll-like receptor 2 (TLR2) pathway. The development of autoimmune diabetes was markedly inhibited in Tlr2(-/-) mice but not in Tlr4(-/-) mice, showing that TLR2 plays an important role in the initiation of the disease. Apoptotic beta-cell injury could stimulate the priming of diabetogenic T cells through a TLR2-dependent, but TLR4-independent, activation of antigen-presenting cells. These findings suggest that beta-cell death and its sensing via TLR2 may be an initial event for the stimulation of antigen-presenting cells and development of autoimmune diabetes.
authors: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors: Hun Sik
authors: HS
authors: Kim
authors: Myoung Sook
authors: MS
authors: Han
authors: Kun Wook
authors: KW
authors: Chung
authors: Sunshin
authors: S
authors: Kim
authors: Eunshil
authors: E
authors: Kim
authors: Myoung Joo
authors: MJ
authors: Kim
authors: Eunkyeong
authors: E
authors: Jang
authors: Hyun Ah
authors: HA
authors: Lee
authors: Jeehee
authors: J
authors: Youn
authors: Shizuo
authors: S
authors: Akira
authors: Myung-Shik
authors: MS
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology
chemical_list: D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4