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Poster presentations: Basic Science 2020

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

E.M. Song, Y.H. Joo, J.Y. Lim, A.R. Choe, C.H. Tae, C.M. Moon, S.E. Kim, H.K. Jung, K.N. Shim, S.A. Jung

Department of Gastroenterology, Ewha Womans University College of Medicine, Seoul, Republic of Korea

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.