Immunomodulatory effect of human umbilical cord mesenchymal stem cells with interleukin-17 receptor-like molecule overexpression on spleen lymphocytes from mice with trinitrobenzene sulfonic acid-induced colitis

AIM: To investigate the immunomodulatory effect of human umbilical cord mesenchymal stem cells with interleukin-17 receptor-like molecule overexpression (IL-17RLM-hUCMSCs) on the spleen lymphocytes from the mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis for providing optimal seed cells to treat inflammatory bowel disease. METHODS: Mesenchymal stem cells were isolated from human umbilical cord. The IL-17RLM gene was transferred into mesenchymal stem cells by lentivirus vector to establish IL-17RLM-hUCMSCs. The experimental colitis mice were induced by TNBS enema, and the spleen lymphocyte suspension was isolated. The lymphocytes were co-cultured with different concentrations of IL-17RLM-hUCMSCs and hUCMSCs under the stimulation of concanavalin A (ConA) for 72 h. The proliferation of lymphocytes was detected by the methods of CCK8 assay and CFSE labeling with lymphocytes+ConA as positive control. The changes of lymphocyte subsets (Th1, Th2, Th17 and Treg) were examined by flow cytometry.RESULTS: Both hUCMSCs and IL-17RLM-hUCMSCs inhibited T-cell proliferation in vitro co-culture system (P < 0.05). When the ratios of MSCs to lymphocytes ranged from 1:1 to 1:10, the inhibitory rates were in a dose-dependent manner. IL-17RLM-hUCMSCs showed higher inhibitory rate than hUCMSCs within the effective concentration range (P < 0.05). Both hUCMSCs and IL-17RLM-hUCMSCs reduced the proportions of Th1 and Th17 cell subsets and increased Treg cell population of spleen lymphocytes from TNBS-induced colitis mice, and IL-17RLM-hUCMSCs showed a stronger inhibitory effect on Th17 cell subset (P < 0.05). CONCLUSION: IL-17RLM-hUCMSCs remarkably inhibit the proliferation of spleen lymphocytes from TNBS-induced colitis mice in a dose-dependent manner. Meanwhile, they regulate immune balance of T cells and have stronger inhibitory effect on Th17 subset.