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

作者：Graham L. Barlow, Christian M. Schürch, Salil S. Bhate, Darci J. Phillips, Arabella Young, Shen Dong, Hunter A Martinez, Gernot Kaber, Nadine Nagy, Sasvath Ramachandran, Janet Meng, Éva Korpos, Jeffrey A. Bluestone, Garry P. Nolan, Paul L. Bollyky · 发表于：eLife · 年份：2025 · DOI：10.7554/elife.100535.3 · 被引用次数：8 · 研究领域：Diabetes and associated disorders、Diabetes Management and Research、Pancreatic function and diabetes

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.