Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus
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. Th...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33011-7 |
| _version_ | 1797836396420923392 |
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| author | Tomoyasu Fukui Tetsuro Kobayashi Erika Jimbo Kaoru Aida Akira Shimada Yoichi Oikawa Yasumichi Mori Takeshi Fujii Rikako Koyama Kazuhiko Kobayashi Akira Takeshita Soroku Yagihashi |
| author_facet | Tomoyasu Fukui Tetsuro Kobayashi Erika Jimbo Kaoru Aida Akira Shimada Yoichi Oikawa Yasumichi Mori Takeshi Fujii Rikako Koyama Kazuhiko Kobayashi Akira Takeshita Soroku Yagihashi |
| author_sort | Tomoyasu Fukui |
| collection | DOAJ |
| description | 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 (2Apro) 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, 2Apro, 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. |
| first_indexed | 2024-04-09T15:09:33Z |
| format | Article |
| id | doaj.art-192035497fce47b4ae7ddaa4acd591c0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T15:09:33Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-192035497fce47b4ae7ddaa4acd591c02023-04-30T11:17:22ZengNature PortfolioScientific Reports2045-23222023-04-0113111610.1038/s41598-023-33011-7Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitusTomoyasu Fukui0Tetsuro Kobayashi1Erika Jimbo2Kaoru Aida3Akira Shimada4Yoichi Oikawa5Yasumichi Mori6Takeshi Fujii7Rikako Koyama8Kazuhiko Kobayashi9Akira Takeshita10Soroku Yagihashi11Division of Immunology and Molecular Medicine, Okinaka Memorial Institute for Medical ResearchDivision of Immunology and Molecular Medicine, Okinaka Memorial Institute for Medical ResearchDivision of Immunology and Molecular Medicine, Okinaka Memorial Institute for Medical ResearchDepartment of Diabetes and Endocrinology, Kanoiwa HospitalDepartment of Endocrinology and Diabetes, Saitama Medical UniversityDepartment of Endocrinology and Diabetes, Saitama Medical UniversityDepartment of Endocrinology and Metabolism, Toranomon HospitalDepartment of Pathology, Toranomon HospitalDepartment of Gastroenterology, Toranomon HospitalGraduate School of Agricultural and Life Sciences, The University of TokyoDepartment of Endocrinology and Metabolism, Toranomon HospitalDepartment of Exploratory Medicine on Nature, Life, and Man, Toho University of MedicineAbstract 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 (2Apro) 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, 2Apro, 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.https://doi.org/10.1038/s41598-023-33011-7 |
| spellingShingle | Tomoyasu Fukui Tetsuro Kobayashi Erika Jimbo Kaoru Aida Akira Shimada Yoichi Oikawa Yasumichi Mori Takeshi Fujii Rikako Koyama Kazuhiko Kobayashi Akira Takeshita Soroku Yagihashi Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus Scientific Reports |
| title | Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus |
| title_full | Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus |
| title_fullStr | Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus |
| title_full_unstemmed | Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus |
| title_short | Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus |
| title_sort | bi glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus |
| url | https://doi.org/10.1038/s41598-023-33011-7 |
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