Interleukin-25 primed mesenchymal stem cells achieve better therapeutic effects on dextran sulfate sodium-induced colitis via inhibiting Th17 immune response and inducing T regulatory cell phenotype.

AIM

This study aimed to investigate the anti-inflammatory mechanism of IL-25 mediated mesenchymal stem cells (MSC) treatment for inflammatory bowel disease (IBD) in a DSS-induced rat colitis model.

METHODS

Rats with DSS-induced colitis were divided into control and treatment groups: normal control group (rats fed with water), DSS group (rats fed with DSS solution), MSC group (DSS-treated rats injected intravenously with GFP-MSCs), IL-25-MSC group (DSS-treated rats injected intravenously with IL-25 primed GFP-MSCs), and mesalazine group (DSS-treated rats fed with mesalazine).

RESULTS

In IL-25-MSC group, therapeutic efficacy (clinical symptoms) was better than in MSC group, but comparable to mesalazine group. In IL-25-MSC group and mesalazine group, fewer infiltrating inflammatory cells and lower pathological score were observed in the intestine. The FOXP3 cells and IL-4 cells decreased, but IL-17A cells and IFN-γ cells increased in the peripheral blood and colonic mucosa after DSS induced colitis, and these phenomena were reversed by MSC or mesalazine treatment. IL-17A cells reduced and FOXP3 cells increased in IL-25-MSC group as compared with MSC group. The expressions of Ki67 and LGR5 were significantly elevated in MSC treatment groups as compared with normal control group, DSS group, and mesalazine group. Definite GFP positive cells were not observed in the intestine of MSC-treated rats.

CONCLUSION

IL-25 primed MSCs exert improved therapeutic effects on the intestinal inflammation of IBD rats which may be related to the inhibition of Th17 immune response and induction of T Regulatory cell phenotype. Thus, IL-25 may be an attractive candidate for MSC-based therapy of IBD.