In vivo, our data show that inflammation- and gut-homing macrophages engineered to overexpress the 1,25(OH)2D-synthesizing enzyme (1α-hydroxylase encoded by the CYP27B1 gene), MAC-CYP cells, increase local expression of the 1α-hydroxylase in inflamed intestines, robustly suppress established experimental colitis, and promote Lgr5+ ISC differentiation. The gene discussed is CYP27B1; the disease is colitis.