BMSCs improve TNBS-induced colitis in rats through inducing Tregs differentiation by expressing PD-L1

Abstract

Objective: Bone marrow-derived mesenchymal stem cells (BMSCs) are a kind of stem cells with high differentiation potential and immunomodulatory ability, which has a broad prospect in the treatment of inflammatory bowel disease. The aim of this study is to investigate whether BMSCs could improve TNBS-induced colitis in Sprague-Dawley (SD) rats through inducing Tregs differentiation by expressing PD-L1.Methods: BMSCs were isolated and identified by flow cytometry before being transfected with PD-L1 siRNA recombinant plasmids. Then SD rats were randomly divided into 4 groups. Colitis induced by TNBS (sigma Aldrich) except normal group. On the fourth day of modeling, the rats in BMSCs control group and PD-L1 siRNA BMSCs group were injected with corresponding BMSCs through tail vein for 1 week, the dose was 5 × 106 cells. The normal group and model group were given the same volume of PBS.Results: PD-L1 siRNA BMSCs and BMSCs could reach colon tissue in TNBS-induced colitis. BMSCs control group significantly improved the clinical symptoms and histopathological severity of TNBS induced colitis, but PD-L1 siRNA BMSCs group did not. We found that the percentage of Tregs in spleen and mesenteric lymph nodes decreased, the expression of PD-L1, IL10, PTEN was down-regulated, and the expression of p-Akt and p-mTOR was up-regulated in colon tissue after PD-L1 siRNA intervention.Conclusion: This study suggested that BMSCs can induce the differentiation of Treg through inhibiting Akt/mTOR pathway by expressing PD-L1, which can significantly improve the symptoms and pathological damage of ulcerative colitis rats and affect the immune function.