biostudies-literatureWang JEUniversity of ChicagoJuvenile Diabetes Research Foundation United States of AmericaNIDDK NIH HHS374https://www.ebi.ac.uk/biostudies/studies/S-EPMC12366006biostudies-literatureUnknown23(1)Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells. Macrophages infiltrate islets early in T1D pathogenesis, preceding the influx of T- and B-lymphocytes. The integrated stress response (ISR), a cellular pathway activated during stress, coordinates adaptive changes in gene expression to maintain cell function and survival. To study the ISR in macrophages, bone-marrow-derived macrophages were treated with a pharmacological inhibitor of the ISR (ISRIB) and polarized to a proinflammatory M1-like state. We observed a reduction in the number of proinflammatory macrophages, as well as a decrease in iNOS mRNA and protein levels, following ISRIB treatment. RNA-sequencing revealed a reduction in pathways related to stress responseCell communication and signaling : CCSThe integrated stress response promotes macrophage inflammation and migration in autoimmune diabetes.PMC12366006R01 DK135832U01 DK127786Quad Summer ScholarshipT32 AI1530203-PDF-2023-1326-A-NMirmira RGPuente AAWang JEMuralidharan CEnriquez JRAnderson RMNargis TTersey SAfalseThe integrated stress response promotes macrophage inflammation and migration in autoimmune diabetes.Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells. Macrophages infiltrate islets early in T1D pathogenesis, preceding the influx of T- and B-lymphocytes. The integrated stress response (ISR), a cellular pathway activated during stress, coordinates adaptive changes in gene expression to maintain cell function and survival. To study the ISR in macrophages, bone-marrow-derived macrophages were treated with a pharmacological inhibitor of the ISR (ISRIB) and polarized to a proinflammatory M1-like state. We observed a reduction in the number of proinflammatory macrophages, as well as a decrease in iNOS mRNA and protein levels, following ISRIB treatment. RNA-sequencing revealed a reduction in pathways related to stress response2025-01-01T00:00:00Z2025 Aug2026-05-29T14:29:53.831Z2026-04-08T05:05:32.454ZS-EPMC123660064083629710.1186/s12964-025-02372-z