TY - JOUR TI - Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/β-catenin signaling in mice AU - Song, Lele AU - Chang, Renxu AU - Sun, Xia AU - Lu, Liying AU - Gao, Han AU - Lu, Huiying AU - Lin, Ritian AU - Xu, Xiaorong AU - Liu, Zhanju AU - Zhan, Lixing T2 - Communications Biology AB - The mucosa microenvironment is critical for intestinal stem cell self-renewal and reconstruction of the epithelial barrier in inflammatory bowel disease (IBD), where the mechanisms underlying cross-talk between intestinal crypts and the microenvironment remain unclear. Here, we firstly identified miR-494-3p as an important protector in colitis. miR-494-3p levels were decreased and negatively correlated with the severity in human IBD samples, as well as in colitis mice. In colitis crypts, a notable cytokine–cytokine receptor, miR-494-3p-targeted EDA2R and the ligand EDA-A2, suppressed colonic stemness and epithelial repair by inhibiting β-catenin/c-Myc. In differentiated IECs, miR-494-3p inhibits macrophage recruitment, M1 activation and EDA-A2 secretion by targeting IKKβ/NF-κB in colitis. A miR-494-3p agomir system notably ameliorated the severity of colonic colitis in vivo. Collectively, our findings uncover a miR-494-3p-mediated cross-talk mechanism by which macrophage-induced intestinal stem cell impairment aggravates intestinal inflammation. DA - 2021/02/16/ PY - 2021 DO - 10.1038/s42003-021-01730-0 DP - www.nature.com VL - 4 IS - 1 SP - 1 EP - 14 LA - en SN - 2399-3642 UR - https://www.nature.com/articles/s42003-021-01730-0 Y2 - 2021/02/16/21:36:50 ER -