Epithelial sensing of vitamin A shapes intestinal antimicrobial defense

REG3 family antimicrobial lectins are prominently induced by the microbiota, but how nutritional cues intersect with microbial signals to regulate their expression is poorly understood. Vitamin A plays a central role in mucosal adaptive immunity, but its contribution to epithelial innate immunity is unclear.

Here, we show that dietary vitamin A promotes expression of REG3 antimicrobial lectins, including REG3G, in intestinal epithelial cells from both mice and humans. Vitamin A–dependent induction of REG3G expression is driven by retinoic acid and requires signaling through retinoic acid receptors (RARs). Mechanistically, RARs directly bind the Reg3g promoter adjacent to a binding site for STAT3, the transcription factor that transduces microbial signals, thereby integrating nutritional and microbial inputs at the level of REG3G transcription.