Epithelial miR‐215 negatively modulates Th17‐dominant inflammation by inhibiting CXCL12 production in the small intestine

MicroRNAs are a class of non‐coding short‐chained RNAs that control cellular functions by downregulating their target genes. Recent research indicates that microRNAs play a role in the maintenance of gut homeostasis. miR‐215 was found to be highly expressed in epithelial cells of the small intestine; however, the involvement of miR‐215 in gut immunity remains unknown. Here, we show that miR‐215 negatively regulates inflammation in the small intestine by inhibiting CXCL12 production. Mice lacking miR‐215 showed high susceptibility to inflammation induced by indomethacin, accompanied by an increased number of Th17 cells in the lamina propria of the small intestine. Our findings provide a rationale for targeting miR‐215 as a therapeutic intervention for inflammatory conditions in the small intestine. miR‐215 is highly and selectively expressed in small intestinal enterocytes. miR‐215 negatively regulates CXCL12 production from the small intestinal epithelium. miR‐215 deficiency exacerbates Th17 inflammation in indomethacin‐induced ileitis.