Open AccessUnique pathological changes in the pancreas of fulminant type 1 diabetes
Author(s) -
Tetsuro Kobayashi,
Shoichiro Tanaka,
Kaoru Aida
Publication year - 2020
Publication title -
diabetology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.411
H-Index - 17
eISSN - 2190-1686
pISSN - 2190-1678
DOI - 10.1007/s13340-020-00462-6
Subject(s) - insulitis , innate immune system , medicine , chemokine , proinflammatory cytokine , paracrine signalling , beta cell , microbiology and biotechnology , autocrine signalling , islet , cxcl10 , pancreas , cancer research , immune system , inflammation , immunology , biology , endocrinology , diabetes mellitus , autoimmunity , receptor
Distinct features of the pancreas of fulminant type 1 diabetes (FT1DM) include (1) enterovirus infection of the islets and exocrine acinar tissue. (2) Activated innate immune responses: MDA5 and RIG-I expression and TLR4 and TLR9 expression in the islets of FT1DM. (3) Combined activation of the STAT/JNK and NFkB pathways, resulting in Type I interferon (IFN) and proinflammatory cytokine (i.e., IFNγ) expression in islet beta cells and MHC class I hyper-expression. (4) Activation of dendritic cells followed by effector cell infiltration of CD8 + T cells and CD68 + macrophages, resulting in apoptosis and neurosis of islet cells and exocrine acinar cells. (5) Many chemo-attractants (i.e., CXCL10) and chemotactic activators (i.e., l-plastin) were induced by a viral infection. (6) Mutual stimulating effect of cytokines expressed in beta cells in autocrine and paracrine mechanisms may enhance beta-cell destruction through the STA1-caspase pathway. (7) Proteomics analysis using laser capture microdissection followed by mass spectrometry found 38 molecules in inflamed islets of FT1DM, which were not highlighted before. Our pathologically verified model of beta-cell destruction in FT1DM will contribute to anti-virus therapy of type 1 diabetes in the near future.