IFNγ and poly(I:C) primed MSCs enhances the therapeutic effects on DSS induced colitis via enhancing indoleamine 2, 3-dioxygenase and inducing regulatory T cell phenotype

Abstract

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine caused by chronic and excessive inflammation. Mesenchymal stem cells (MSCs) are pluripotent cells with immunosuppressive properties, currently studied as a potential treatment for IBD. We previously demonstrated that among various TLR ligands, MSCs treated with poly(I:C), which is a TLR3 ligand, more profoundly induced IDO, which is a therapeutically relevant immunosuppressive factor, without any observable phenotype change in vitro. The goal of the study was to determine whether poly(I:C) can enhance the therapeutic efficacy of bone marrow-derived MSCs for the treatment of IBD. To compare the therapeutic effects between naïve MSCs and primed MSCs by poly(I:C) stimulation on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index (DAI) score and body weight loss were significantly improved in the primed MSCs treated mice group. Also the pathologic severity of colon were more recovered in primed MSCs treated group. The frequency of T cells in spleen and mesenteric lymph node was markedly decreased in primed MSCs treated group. Foxp3 expressing regulatory T cells were more expanded in primed MSCs treated group. Treatment of primed MSCs reduced the expression of proinflammatory cytokines in colon tissue. In conclusion, we demonstrate that primed MSCs with poly(I:C) improve their efficacy in treating DSS-induced colitis, and this effect at least partly depends on the enhancement of their immunosuppressive activity through increasing their production of IDO.