Targeting persistent necroptotic-to-apoptotic epithelial signaling in IBD

Targeting the necroptotic-to-apoptotic epithelial death axis could promote deeper remission in IBD by blocking a pathogenic program that persists despite advanced therapy. Patient biopsies and human intestinal models showed that early inflammation drives an M1 macrophage-like epithelial state with RIPK1-independent necroptotic signaling, followed by NOS2-mediated mitochondrial apoptosis of absorptive cells and PUMA-mediated intestinal stem cell death. Aberrant cell-death signaling was detectable in remission and predicted relapse, identifying a mechanism not fully suppressed by current therapies...