Nestin+ Peyer's patch resident MSCs enhance healing of inflammatory bowel disease through IL-22-mediated intestinal epithelial repair

Abstract

Inflammatory bowel disease (IBD) is a chronic condition characterized by gastrointestinal tract inflammation and still lacks satisfactory treatments. Mesenchymal stromal cells (MSCs) show promising potential for treating IBD, but their therapeutic efficacy varies depending on the tissue of origin. We aim to investigate whether intestine Peyer's patch (PP)-derived MSCs have superior immunomodulatory effects on T cells and better therapeutic effects on IBD compared with bone marrow-derived MSCs. We isolated PPs-derived Nestin+ MSCs (MSCs^PP) and bone marrow-derived Nestin+ MSCs (MSCs^BM) from Nestin-GFP transgenic mice to explore their curative effects on murine IBD model. Moreover, we tested the effects of IL-22 knockdown and IL-22 overexpression on the therapeutic efficacy of MSCs^PP and MSCs^BM in murine IBD, respectively. We demonstrated that Nestin+ cells derived from murine PPs exhibit MSC-like biological characteristics. Compared with MSCs^BM, MSCs^PP possess enhanced immunoregulatory ability to suppress T cell proliferation and inflammatory cytokine production. Moreover, we observed that MSCs^PP exhibited greater therapeutic efficacy than MSCs^BM in murine IBD models. Interestingly, IL-22, which was highly expressed in MSCs^PP, could alleviate the severity of the intestinal inflammation, while knockdown IL-22 of MSCs^PP remarkably weakened the therapeutic effects. More importantly, IL-22 overexpressing MSCs^BM could significantly improve the symptoms of murine IBD models. This study systemically demonstrated that murine MSCs^PP have a prominent advantage in murine IBD treatment, partly through IL-22.