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Natural protection from type 1 diabetes in Non Obese Diabetic (NOD) mice is characterised by a unique pancreatic islet phenotype

View ORCID ProfileJoanne Boldison, Terri C. Thayer, Joanne Davies, View ORCID ProfileF. Susan Wong
doi: https://doi.org/10.1101/2021.01.10.426116
Joanne Boldison
1Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
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  • For correspondence: Boldisonj@Cardiff.ac.uk J.boldison@exeter.ac.uk
Terri C. Thayer
1Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
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Joanne Davies
1Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
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F. Susan Wong
1Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
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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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 10, 2021.
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Natural protection from type 1 diabetes in Non Obese Diabetic (NOD) mice is characterised by a unique pancreatic islet phenotype
Joanne Boldison, Terri C. Thayer, Joanne Davies, F. Susan Wong
bioRxiv 2021.01.10.426116; doi: https://doi.org/10.1101/2021.01.10.426116
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Natural protection from type 1 diabetes in Non Obese Diabetic (NOD) mice is characterised by a unique pancreatic islet phenotype
Joanne Boldison, Terri C. Thayer, Joanne Davies, F. Susan Wong
bioRxiv 2021.01.10.426116; doi: https://doi.org/10.1101/2021.01.10.426116

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