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, Ki Nam Shim

Research output: Contribution to journalArticlepeer-review

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 com-paring 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.

Original languageEnglish
Pages (from-to)917-930
Number of pages14
JournalKorean Journal of Internal Medicine
Volume39
Issue number6
DOIs
StatePublished - Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 The Korean Association of Internal Medicine.

Keywords

  • Colitis model
  • Colonic mucosa
  • Human colonic tissues
  • Inflammatory bowel disease

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