Islet amyloid disrupts MHC class II antigen presentation and delays autoimmune diabetes in NOD mice – Published online 22/12/2025

Heather C. Denroche, Victoria Ng, Jane Velghe, Imelda Suen, Liam Stanley, Dominika Nackiewicz, Mitsuhiro Komba, Derek L. Dai, Galina Soukhatcheva, Sam Chen, C. Bruce Verchere

Islet amyloid is best known for its harmful effects on beta cells in type 2 diabetes, where it promotes inflammation and beta cell dysfunction. In this study, Denroche et al (https://doi.org/10.1007/s00125-025-06622-0) reveal an unexpected role for islet amyloid in beta cell autoimmunity. Using complementary transgenic and knock-in mouse models, the authors show that early amyloid formation in pancreatic islets reduces MHC class II antigen presentation by local antigen-presenting cells and delays diabetes onset. Rather than impairing systemic immune function or enabling beta cells to evade immune recognition, phagocytosis of islet amyloid by antigen-presenting cells impairs activation of antigen-specific CD4 T cells. These findings challenge the prevailing view of islet amyloid as uniformly pathogenic and reveal an additional way in which islet amyloid can shape interactions between beta cells and the immune system. The authors conclude that, in light of recent evidence of islet amyloid in type 1 diabetes, this work provides timely insight into its potential role in autoimmune disease.

 

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