title: Pathological changes in the pancreas of fulminant type 1 diabetes and slowly progressive insulin-dependent diabetes mellitus (SPIDDM): innate immunity in fulminant type 1 diabetes and SPIDDM.
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.
  
  
  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.
authors: Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan. tetsurou@yamanashi.ac.jp
authors: Tetsuro
authors: T
authors: Kobayashi
authors: Yoriko
authors: Y
authors: Nishida
authors: Shoichiro
authors: S
authors: Tanaka
authors: Kaoru
authors: K
authors: Aida
mesh_terms: D000293:Adolescent; D000328:Adult; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D016883:Diabetic Ketoacidosis / Q000401:mortality; D018450:Disease Progression; D004769:Enterovirus Infections / Q000150:complications; D006801:Humans; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010179:Pancreas / Q000473:pathology*; D020365:RNA Helicases / Q000096:biosynthesis; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors / Q000096:biosynthesis; D015678:Viral Structural Proteins / Q000096:biosynthesis
chemical_list: D016898:Interferon-alpha; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D015678:Viral Structural Proteins; D016899:Interferon-beta; C520569:DHX58 protein, human; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases