Bi-glandular and Persistent Enterovirus Infection and Distinct Changes of the Pancreas in Slowly Progressive Type 1 Diabetes Mellitus

Overview

Journal Sci Rep

Specialty Science

Date 2023 Apr 28

PMID 37117225

Authors

Tomoyasu Fukui

Tetsuro Kobayashi

Erika Jimbo

Kaoru Aida

Akira Shimada

Yoichi Oikawa

Yasumichi Mori

Takeshi Fujii

Rikako Koyama

Kazuhiko Kobayashi

Akira Takeshita

Soroku Yagihashi

Affiliations

Soon will be listed here.

Abstract

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2A) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2A, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3 T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.

Citing Articles

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Slowly progressive insulin-dependent diabetes mellitus in type 1 diabetes endotype 2.

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