RIPK1 regulates beta-cell fate and autoimmunity in type 1 diabetes

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic beta-cells. RIPK1, a key regulator of cell death and inflammation, has been implicated in beta-cell responses to cytokines and immune attack. To investigate RIPK1's role in beta-cell fate during autoimmune stress, we generated CRISPR/Cas9-mediated Ripk1-deleted NIT-1 beta-cells and exposed them to TNFα+IFNγ or self-reactive diabetic NOD splenocytes. Using RNA-seq, kinome profiling, flow cytometry, and small molecule inhibitors, we demonstrate that RIPK1 deletion or pharmacological inhibition protects beta-cells from cytokine-induced and autoimmune cell death. This study provides insights into RIPK1-dependent pathways in beta-cell vulnerability and suggests potential therapeutic strategies for T1D.