title: Toll-like receptors, the NLRP3 inflammasome, and interleukin-1β in the development and progression of type 1 diabetes.
abstract: Traditionally, type 1 diabetes (T1D) has been thought of as a disease of cellular immunity, but there is increasing evidence that components of the innate immune system, controlled largely by Toll-like receptors (TLRs), play a significant role in T1D development. TLRs are pattern-recognition molecules on immune cells that recognize pathogens, leading to the production of cytokines such as interleukin-1β (IL1β, encoded by the IL1B gene). IL1β is increased in patients with newly diagnosed T1D and likely acts as an early inflammatory signal in T1D development. Because hyperglycemia is a hallmark of T1D, the effects of hyperglycemia on IL1β expression in peripheral blood mononuclear cells (PBMCs) and islet cells have been examined, but with inconsistent results, and the mechanisms leading to this increase remain unknown. Fatty acids stimulate IL1β expression and may promote inflammation, causing hyperglycemia and insulin resistance. The mechanisms by which IL1β is involved in T1D pathogenesis are controversial. Overall, studies in pancreatic β-cells suggest that IL1β-mediated damage to islet cells involves multiple downstream targets. Potential therapies to decrease the progression of T1D based on IL1β biology include pioglitazone, glyburide, IL1 receptor antagonists, and agents that remove IL1β from the circulation.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA. ellen.grishman@childrens.com
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Grishman
authors.forename: Perrin C
authors.initials: PC
authors.lastname: White
authors.forename: Rashmin C
authors.initials: RC
authors.lastname: Savani
mesh_terms: D002352:Carrier Proteins / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D018450:Disease Progression; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D058847:Inflammasomes / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D051193:Toll-Like Receptors