P049 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 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 sulfate (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(ug) 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.