Department of Clinical Laboratory, Shanxi Provincial People's Hospital, Taiyuan, China.
The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, China.
PeerJ. 2023 May 31;11:e15481. doi: 10.7717/peerj.15481. eCollection 2023.
To investigate the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1) in the mucosal tissues and peripheral blood of patients with ulcerative colitis (UC).
Eighty patients with UC were recruited from January 2021 to August 2022 from the Shanxi Province People's Hospital. PD-1 and PD-L1 expression was assessed by immunohistochemistry in mucosal tissues. An enzyme-linked immunosorbent assay was used to measure soluble PD-1 and PD-L1 levels in peripheral blood serum, and the membrane-bound forms of PD-1 (mPD-1), (T-helper cell) Th1 and Th17, in peripheral blood were determined by flow cytometry.
PD-1 expression was observed only in the monocytes of the mucosal lamina propria of UC patients, while PD-L1 was mainly located in both epithelial cells and monocytes on the cell membrane. The expression level of PD-1/PD-L1 in the monocytes and epithelial cells of mucosal lamina propria increased with disease activity ( < 0.05). The percentages of PD-1/T and PD-1/CD4+T in the peripheral blood of moderate UC patients (PD-1/T 12.83 ± 6.15% and PD-1/CD4+T 19.67 ± 9.95%) and severe UC patients (PD-1/T 14.29 ± 5.71% and PD-1/CD4+T 21.63 ± 11.44%) were higher than in mild UC patients (PD-1/T 8.17 ± 2.80% and PD-1/CD4+T 12.44 ± 4.73%; < 0.05). There were no significant differences in PD-1/CD8+T cells between mild and severe UC patients ( > 0.05). There was a statistically significant difference in the expression level of sPD-L1 between the UC groups and healthy controls, and the expression level of sPD-L1 increased with disease severity ( < 0.05); however, there was no statistically significant difference in sPD-1 expression levels between the UC groups and healthy controls ( 0.05). The correlation coefficients between Th1 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.427, 0.589, 0.486, and 0.329, respectively ( < 0.001). The correlation coefficients between Th17 and sPD-L1, PD-1/T, PD-1/CD4+T and PD-1/CD8+T were 0.323, 0.452, 0.320, and 0.250, respectively ( < 0.05).
The expression level of PD-1/PD-L1 was correlated with UC disease activity, and two forms of PD-1 and PD-L1 may be used as a potential marker for predicting UC and assessing disease progression in UC patients. PD-1/PD-L1 imbalance was a significant phenomenon of UC immune dysfunction. Future research should focus on two forms of PD-1/PD-L1 signaling molecules to better understand the pathogenesis of UC and to identify potential drug therapies.
探讨程序性死亡蛋白 1(PD-1)和程序性死亡配体 1(PD-L1)在溃疡性结肠炎(UC)患者黏膜组织和外周血中的表达及意义。
2021 年 1 月至 2022 年 8 月,山西省人民医院招募了 80 名 UC 患者。采用免疫组织化学法检测黏膜组织中 PD-1 和 PD-L1 的表达。采用酶联免疫吸附试验检测外周血血清中可溶性 PD-1 和 PD-L1 水平,采用流式细胞术检测外周血中 PD-1(T 辅助细胞)Th1 和 Th17 的膜结合形式(mPD-1)。
PD-1 仅在 UC 患者黏膜固有层的单核细胞中表达,而 PD-L1 主要位于上皮细胞和细胞膜上的单核细胞中。黏膜固有层单核细胞和上皮细胞中 PD-1/PD-L1 的表达水平随疾病活动度增加而升高(<0.05)。中度 UC 患者(PD-1/T 12.83±6.15%和 PD-1/CD4+T 19.67±9.95%)和重度 UC 患者(PD-1/T 14.29±5.71%和 PD-1/CD4+T 21.63±11.44%)外周血中 PD-1/T 和 PD-1/CD4+T 的百分比高于轻度 UC 患者(PD-1/T 8.17±2.80%和 PD-1/CD4+T 12.44±4.73%;<0.05)。轻度和重度 UC 患者之间 PD-1/CD8+T 细胞无显著差异(>0.05)。UC 组与健康对照组之间 sPD-L1 的表达水平存在统计学差异,且随着疾病严重程度的增加而升高(<0.05);然而,UC 组与健康对照组之间 sPD-1 的表达水平无统计学差异(>0.05)。Th1 与 sPD-L1、PD-1/T、PD-1/CD4+T 和 PD-1/CD8+T 的相关系数分别为 0.427、0.589、0.486 和 0.329(<0.001)。Th17 与 sPD-L1、PD-1/T、PD-1/CD4+T 和 PD-1/CD8+T 的相关系数分别为 0.323、0.452、0.320 和 0.250(<0.05)。
PD-1/PD-L1 的表达水平与 UC 疾病活动度相关,两种形式的 PD-1 和 PD-L1 可能作为预测 UC 和评估 UC 患者疾病进展的潜在标志物。PD-1/PD-L1 失衡是 UC 免疫功能障碍的一个显著现象。未来的研究应集中于两种形式的 PD-1/PD-L1 信号分子,以更好地了解 UC 的发病机制,并确定潜在的药物治疗方法。