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The extra-islet pancreas supports autoimmunity in human type 1 diabetes.

The extra-islet pancreas supports autoimmunity in human type 1 diabetes. eLife Barlow, G. L., Schürch, C. M., Bhate, S. S., Phillips, D. J., Young, A., Dong, S., Martinez, H. A., Kaber, G., Nagy, N., Ramachandran, S., Meng, J., Korpos, E., Bluestone, J. A., Nolan, G. P., Bollyky, P. L. 2025; 13

Abstract

In autoimmune type 1 diabetes (T1D), immune cells infiltrate and destroy the islets of Langerhans - islands of endocrine tissue dispersed throughout the pancreas. However, the contribution of cellular programs outside islets to insulitis is unclear. Here, using CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples, we simultaneously examine islet and extra-islet inflammation in human T1D. We identify four sub-states of inflamed islets characterized by the activation profiles of CD8+T cells enriched in islets relative to the surrounding tissue. We further find that the extra-islet space of lobules with extensive islet-infiltration differs from the extra-islet space of less infiltrated areas within the same tissue section. Finally, we identify lymphoid structures away from islets enriched in CD45RA+ T cells - a population also enriched in one of the inflamed islet sub-states. Together, these data help define the coordination between islets and the extra-islet pancreas in the pathogenesis of human T1D.

View details for DOI 10.7554/eLife.100535

View details for PubMedID 40232951

View details for PubMedCentralID PMC11999700