Role of innate immunity in triggering and tuning of autoimmune diabetes.
Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cells (APCs) to beta-cell antigens to almost total insulin deficiency due to islet destruction. Although it is established that the interaction of environmental factors with genetic traits plays a pivotal role in the pathogenesis of T1D, in most cases, the exact trigger of anti-islet autoimmunity and how genetic and environmental factors regulate its progression, ultimately leading to the development of T1D remain elusive. In this review, based on the recent advances in understanding the role of innate immunity in development of autoimmune diseases, we focus on the possibility that aberrant regulation of the innate immune system frequently observed in animal models and patients with T1D, induces T1D by triggering anti-islet autoimmunity in the context of the autoimmune-prone environment; this information might provide an insight into possibilities for therapeutic intervention modulating innate immunity to mitigate or prevent T1D.
Kim
Hun Sik
HS
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Myung-Shik
MS
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D004777:Environment; D006801:Humans; D007113:Immunity, Innate; D050417:Insulin-Secreting Cells / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats; D011913:Rats, Inbred BB; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
D051193:Toll-Like Receptors