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Natural protection from Type 1 Diabetes in Non obese diabetic (Nod) mice is characterised by a unique pancreatic islet phenotype

Boldison, Joanne, Thayer, Terri C., Davies, Joanne and Wong, F. Susan 2021. Natural protection from Type 1 Diabetes in Non obese diabetic (Nod) mice is characterised by a unique pancreatic islet phenotype. Diabetes 70 (3) , db200945. 10.2337/db20-0945

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Abstract

The non-obese diabetic (NOD) mouse develops spontaneous type 1 diabetes, with some features of disease that are very similar to the human disease. However, a proportion of NOD mice are naturally-protected from developing diabetes, and currently studies characterising this cohort are very limited. Here, using both immunofluorescence and multi-parameter flow cytometry we focus on the pancreatic islet morphology and immune infiltrate observed in naturally-protected NOD mice. We show that naturally-protected NOD mice are characterised by an increased frequency of insulin-containing, smaller sized, pancreatic islets. Although mice remain diabetes free, florid immune infiltrate remains. However, this immune infiltrate is skewed towards a regulatory phenotype in both T and B-cell compartments. Pancreatic islets have an increased frequency of IL-10 producing B cells and associated cell surface markers. Resident memory CD69+CD8+ T cells show a significant shift towards reduced CD103 expression, while CD4+ T cells have increased FoxP3+CTLA4+ expression. These data indicate that naturally-protected NOD mice have a unique islet signature and provide new insight into regulatory mechanisms within pancreatic islets.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Diabetes Association
ISSN: 0012-1797
Date of First Compliant Deposit: 4 March 2021
Date of Acceptance: 25 January 2021
Last Modified: 07 Jan 2022 06:13
URI: http://orca.cardiff.ac.uk/id/eprint/139275

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