Unique Inflammatory Changes in Exocrine and Endocrine Pancreas in Enterovirus-induced Fulminant Type 1 Diabetes

Context: There is scant
report 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 the diabetes in FT1DM.

Method: The exocrine
and endocrine pancreases of 3 FT1DM and 17 non-diabetic 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) expression.

Results:
The
median frequency of insulitis, observed in all FT1DM pancreases, was 67%. In
non-diabetic 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 in 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 in the control group.
Infiltrating CD8+ T cells, CD68+ macrophages and CD11c+ dendritic cells were
observed around exocrine acinar cells in FT1DM. VP1 and CXCL10 were detected in
islet cells as well as exocrine cells in FT1DM. CXCL10 positive exocrine cells
were surrounded by CXCR3+ T cells.

Conclusion: The
pathological findings suggested that suppression of activated CXCL10-CXCR3 axis
in exocrine as well as endocrine pancreas is a new therapeutic target in FT1DM
and possibly in enter virus associated acute-onset type1 diabetes.

Precis:This study reports
the association between exocrine pancreas damage and enterovirus infection in
fulminant type 1 diabetes(FT1DM).Importanat factors identified in the pancreas
of FT1DM were enterovirus infection,inflammation involving
chemokine/cytokine(CXCL10/CXCR3) network and apoptosis/necrosis of the
pancreatic exocrine cells and islet cells.