Gliadin amplifies the macrophage response triggered by stressed beta cells

In humans, a gluten-free diet can slow disease progression and improve clinical outcome in newly diagnosed type 1 diabetes patients. In NOD mice, the incidence of autoimmune diabetes is influenced by both beta cell activity and gluten. Here, we demonstrate that metabolically stressed pancreatic cell lines (MIN6, beta TC3, and alpha TC3) effectively activated macrophage RAW 264.7 cells. Gliadin further enhanced this response in MIN6 cells but had no such effect on beta TC3 or alpha TC3 cells. Additionally, gliadin directly stimulated MIN6 cells, affecting pathways related to cellular activation, stress responses, and immune regulation. These findings provide insights into the in vivo benefits of a gluten-free diet in type 1 diabetes development by highlighting the roles of cellular stress and gliadin in disease progression.