posted on 2021-02-02, 19:19authored byJoanne Boldison, Terri C. Thayer, Joanne Davies, F. Susan Wong
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.
Funding
This work was funded by the Medical Research Council (UK) MR/K021141/1