| The role of PD-1/PD-L1 pathway in ulcerative colitis and changes following tonsil-derived mesenchymal stem cells treatment |
Eun Mi Song, Yang Hee Joo, Sung-Ae Jung
, Ju-Ran Byeon, A-Reum Choe, Yehyun Park, Chung Hyun Tae, Chang Mo Moon, Seong-Eun Kim, Hye-Kyung Jung, and Ki-Nam Shim |
| Department of Internal Medicine, College of Medicine, Ewha Womans University, Ewha Medical Research Institute, Seoul, Korea |
Corresponding Author:
Sung-Ae Jung , Tel: +82-2-6986-1620, Fax: +82-2-6986-3129, Email: jassa@ewha.ac.kr
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Received: January 16, 2024; Revised: June 4, 2024; Accepted: June 16, 2024. |
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| Abstract |
Background/Aims: The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has not been fully evaluated in inflammatory bowel disease. We evaluated PD-1/PD-L1 levels in patients with ulcerative colitis (UC) and their significance in tonsil-derived mesenchymal stem cells (TMSCs) treatment.
Methods: Using acute and chronic murine colitis model, we measured the PD-1 and PD-L1 levels in inflamed colonic tissues pre- and post-treatment with TMSCs. We also measured PD-1 and PD-L1 levels in colonic tissues from UC patients, compared to normal controls.
Results: In the analysis using human colonic tissues, a significant increase in the levels of PD-1 and PD-L1 was observed in the colonic mucosa of patients with UC compared with normal controls (p < 0.001 and p = 0.005, respectively). When comparing the maximal disease extent, PD-L1 levels were highest in patients with proctitis (38.5 ± 46.7), followed by left-side colitis (17.5 ± 23.1) and extensive colitis (5.2 ± 8.2) (p < 0.001). In the chronic colitis model, the level of PD-L1 was decreased (p = 0.040) and the level of PD-1 increased more than in normal controls (p = 0.047). After treatment with TMSC, significant improvements were observed in body weight, disease activity index, and colon length recovery. Additionally, the levels of PD-1 and PD-L1 were recovered; PD-L1 significantly increased (p = 0.031), while the level of PD-1 decreased (p = 0.310).
Conclusions: The altered expression of PD-1 and PD-L1 in colonic mucosa may be a possible mechanism of UC, and T-MSC-derived PD-L1 could help suppress colitis. |
| Keywords:
Colitis model ; Colonic mucosa ; Human colonic tissues ; Inflammatory bowel disease |
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