Decoding the IBD paradox: A triadic interplay between REG3, enterococci, and NOD2

In this issue of Cell Host & Microbe, Jang et al. decode an intriguing paradox: excessive antimicrobial peptide-regenerating family member 3 (REG3) expression in inflammatory bowel disease (IBD) patients depletes protective enterococci. This depletion impairs the NOD2 anti-inflammatory pathway and perpetuates inflammation, thus providing insight into IBD pathogenesis.