Unique Inflammatory Changes In Exocrine And Endocrine Pancreas In Enterovirus-Induced Fulminant Type 1 Diabetes
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM(2019)
摘要
Context: There are scant reports on the pathological changes of the exocrine and endocrine pancreas in fulminant type 1 diabetes mellitus (FT1DM).Objective: To clarify the distinct pathological changes in the exocrine as well as the endocrine pancreas shortly after onset of diabetes in FT1DM.Design: The exocrine and endocrine pancreases of 3 patients with FT1DM and 17 nondiabetic controls were immunohistochemically examined for islet and exocrine tissue inflammation, infiltrating mononuclear cell (MNC) CD subtype, enterovirus capsid protein 1 (VP1) localization, and CXC chemokine ligand 10 (CXCL10) and CXC chemokine receptor 3 (CXCR3) expressions.Results: The median frequency of insulitis in the 3 FT1DM pancreases was 60%. In the nondiabetic control pancreases, no insulitis was observed. In the islets of FT1DM, the numbers of CD45(+), CD3(+), CD8(+), CD68(+), and CD11c(+) MNCs were significantly higher than those of the control group. In the exocrine pancreas of FT1DM, the numbers of CD3(+) T cells, CD8(+) T cells, CD68(+) macrophages, and CD11c(+) dendritic cells were significantly higher than those of the control group. Infiltrating CD8(+) T cells, CD68(+) macrophages, and CD11c(+) dendritic cells were observed around exocrine acinar cells in FT1DM. There was a close association between VP1 and CXCL10 expression in pancreatic exocrine ductal cells and acinar cells as well as islet cells in FT1DM. CXCL10(+) exocrine cells were surrounded by CXCR3(+) T cells.Conclusion: The pathological findings suggested that suppression of the activated CXCL10-CXCR3 axis in the exocrine as well as the endocrine pancreas is a novel therapeutic target in FT1DM and possibly in enterovirus-associated acute-onset type 1 diabetes.
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