Beyond bystanders: How β cell stress shapes the autoimmune response in T1D

For many years, research focused on the immune system’s role in the development of type 1 diabetes (T1D). However, mounting evidence suggests a critical involvement of intrinsic pancreatic β cell defects, particularly impaired cellular stress responses, in disease pathology. This shift in understanding is supported by the limited effectiveness of immune-targeting therapies, which have so far managed to delay, rather than prevent or cure, T1D. Here, we discuss why the immune system specifically targets β cells, how stress pathways modify the interaction between β cells and immune cells, β cell resilience, and challenges and opportunities in targeting β cell stress in T1D.