Abstract
Objective
The contribution of innate immunity responsible for beta‐cell destruction in fulminant type 1 diabetes (FT1D) and slowly progressive insulin‐dependent diabetes mellitus (SPIDDM) is unclear.
Research Design and Methods
Islet‐cell expression of Toll‐like receptors (TLRs) including TLR3 and TLR4, the cytoplasmic retinoic acid‐inducible protein I (RIG‐I)‐like helicases, RIG‐I, melanoma differentiation‐associated gene‐5 and laboratory of genetics and physiology 2 in the affected islets were studied immuno‐histochemically on three pancreases obtained 2–5 days after the onset of FT1D and a pancreas from a patient with SPIDDM.
Results
Laboratory of genetics and physiology 2 and RIG‐I strongly expressed in beta cells in all three FT1D pancreases infected with enterovirus (VP1 antigen). Melanoma differentiation‐associated gene‐5 was hyper‐expressed in all subsets of islet cells including beta cells and alpha cells. TLR3 and TLR4 were expressed in mononuclear cells that infiltrated to islets. IFN‐alpha/beta was strongly expressed in islet cells. In contrast, pancreas of a patient with SPIDDM, enterovirus and expression of innate immune receptors including RIG‐I, melanoma differentiation‐associated gene‐5, hyperexpression of laboratory of genetics and physiology 2 and mononuclear cells, which were positive for TLR3 and TLR4, and infiltration to the islets were not detected.
Conclusions
These findings demonstrate that retinoic acid‐inducible protein I (RIG‐I)‐like helicases and TLRs play a crucial role on beta‐cell destruction in enterovirus‐induced FT1D. The presence of distinct mechanism(s) of slowly progressive beta‐cell failure in SPIDDM was suggested. Copyright © 2011 John Wiley & Sons, Ltd.