In this study, we found that Nestin can be used as a marker for identifying murine PP‐resident MSCs and then demonstrated that PP‐derived Nestin+ MSCs (MSCsPP) were more effective than bone marrow‐derived Nestin+ MSCs (MSCsBM) in treating murine inflammatory bowel disease, which was realized partially through interleukin 22 (IL‐22)‐mediated regulation of mucosal homeostasis. The gene discussed is NES; the disease is inflammatory bowel disease.