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 Jieying Chen and Jing Huang contributed equally to this study.

Research advancements and perspectives of inflammatory bowel disease: A comprehensive review

“… 110 Peyer's patch-derived Nestin + MSCs have a superior therapeutic potency in the treatment of murine IBD. 111 Human umbilical cord-derived MSCs promote the proliferation of type 1 regulatory T cells in an indoleamine-2,3-dioxygenase-dependent manner to alleviate TNBS-induced colitis. 112 FMT is a promising treatment for IBD, by which the gut microbiota is transplanted from healthy donors to patients, and the efficacy may rely on the interplay of gut microbiota between donors and recipients.…”

Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis

“… 116 PP-derived mesenchymal stromal cells (MSCs) perform enhanced immunomodulatory capacities and inhibit the abnormal proliferation of T-cells as well as the production of inflammatory factors. 117 Robo4 is also a regulator of the vascular endothelial barrier during pancreatic inflammation, which could induce the renewal and regeneration of B-cells in PPs, 118 , 119 while, subsequent transcriptomics data are needed in terms of SAP-ALI.…”