Korean J Intern Med.  2024 Nov;39(6):917-930. 10.3904/kjim.2024.019.

The role of PD-1/PD-L1 pathway in ulcerative colitis and changes following tonsil-derived mesenchymal stem cells treatment

• Song EM
• Joo YH
• Jung SA
• Byeon JR
• Choe AR
• Park Y
• Tae CH
• Moon CM
• Kim SE
• Jung HK
• Shim KN

• KMID: 2560513
• DOI: http://doi.org/10.3904/kjim.2024.019

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.

Keyword

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