P103 The treatment effect of tonsil-derived mesenchymal stem cells (T-MSCs) via regulating programmed death-1/programmed death ligand-1 (PD-1/PD-L1) in ulcerative colitis

Abstract

Abstract Background The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has not been fully evaluated in inflammatory bowel disease. We evaluated the level of PD-1/PD-L1 in the mucosa of patients with ulcerative colitis and revealed the role of PD-1/PD-L1 in the immunomodulatory mechanism of tonsil-derived mesenchymal stem cells (T-MSCs). Methods We used chronic murine colitis model induced by dextran sodium sulphate (DSS). We measured the PD-1 and PD-L1 levels in inflamed colonic tissues before and after the treatment with T-MSC. We also measured the levels of PD-1 and PD-L1 in the colonic tissues from patients with ulcerative colitis and compared with those from normal controls. Results In chronic colitis model, the level of PD-L1 was decreased than normal controls (fold change) (1.0 vs. 0.46 ± 0.08, p = 0.05). However, the level of PD-1 was increased than normal controls (1.0 vs. 6.84 ± 8.16, p = 0.142). After treatment with T-MSC which showed significant improvement in body weight, disease activity index and colon length, the levels of PD-1 and PD-L1 were recovered; PD-L1 was significantly increased (1.04 ± 0.77 vs. 0.46 ± 0.08, p = 0.031) and the level of PD-1 was decreased (3.63 ± 1.94 vs. 6.84 ± 8.16, p = 0.537). When measuring the level of PD-1 and PD-L1 in both soluble medium and cell lysate of T-MSC, we found that the PD-1 and PD-L1 were expressed in both forms (182.63 pg/ml in soluble medium and 11.85 pg/protein (μg) in cell lysate after 7 days of differentiation period). In the analysis using human colonic tissues, a significantly increase in the levels of PD-1 and PD-L1 was observed in the colonic mucosa of patients with UC compared with normal controls (PD-1: 2.09 ± 3.95 vs. 7.93 ± 14.21, p = 0.034 and PD-L1: 2.24 ± 2.91 vs. 10.08 ± 18.13, p = 0.044). Conclusion The altered expression of PD-1 and PD-L1 in colonic mucosa may a possible mechanism of ulcerative colitis and T-MSC-derived PD-L1 could repress the colitis.