Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China; Institute of Psoriasis, Tongji University School of Medicine, Shanghai 200072, China; Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Institute of Psoriasis, Tongji University School of Medicine, Shanghai 200072, China; Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Int Immunopharmacol. 2021 Jul;96:107722. doi: 10.1016/j.intimp.2021.107722. Epub 2021 May 6.
Psoriasis is a T cell-mediated autoimmune skin disease. Accumulating evidence has demonstrated that co-inhibitory receptors (CIRs) play a vital role in regulating T cell-mediated immune response, especially in neoplasm and autoimmunity. However, the immuno-function of CIRs in the development of psoriasis remains unclear.
We investigated the expression of CIRs on the circulating T lymphocytes of psoriasis patients before and after anti-tumor necrosis factor-α (TNF-α) therapy.
We enrolled 17 patients with moderate-to-severe plaque psoriasis, 17 patients with mild plaque psoriasis, and 18 healthy controls in this study. Fourteen of the moderate-to-severe psoriasis patients were treated with infliximab, a monoclonal antibody against TNF-α. Peripheral blood was collected, and peripheral blood mononuclear cells were extracted. The proportion of T cell subsets along with their expression of CIRs, namely T cell immunoreceptor with Ig and ITIM domains (TIGIT), lymphocyte activating gene 3 (LAG-3), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), B and T lymphocyte-associated protein (BTLA), endothelial protein C receptor (PROCR), podoplanin (PDPN), programmed cell death 1 (PD-1), and T cell immunoglobulin mucin family containing molecule 3 (TIM-3), were determined by flow cytometric assay.
The moderate-to-severe plaque psoriasis patients had less circulating Tregs, which increased after infliximab treatment. They also had decreased TIGIT, LAG-3 but increased PDPN expression on peripheral CD4 T cells. Infliximab enhanced TIGIT, LAG-3, CTLA-4 but reduced PROCR expression on circulating CD4 T cells. Remarkably, both the frequency of circulating Tregs and the expression level of TIGIT on CD4 T cells at baseline (pre-treatment) negatively correlated with the extent of PASI score reduction benefited from infliximab therapy.
Anti-TNF-α therapy increased the frequency of Tregs and TIGIT, LAG-3, CTLA-4 expression but reduced PROCR expression on circulating CD4 T cells in psoriasis patients. The baseline proportion of Tregs and the expression level of TIGIT on circulating CD4 T cells might serve as predictive markers for the degree of disease remission benefited from infliximab treatment.
银屑病是一种 T 细胞介导的自身免疫性皮肤病。越来越多的证据表明，共抑制受体（CIRs）在调节 T 细胞介导的免疫反应中起着至关重要的作用，尤其是在肿瘤和自身免疫中。然而，CIRs 在银屑病发展中的免疫功能仍不清楚。
我们研究了抗肿瘤坏死因子-α（TNF-α）治疗前后银屑病患者循环 T 淋巴细胞中 CIRs 的表达。
我们纳入了 17 例中重度斑块状银屑病患者、17 例轻度斑块状银屑病患者和 18 例健康对照者。14 例中重度银屑病患者接受英夫利昔单抗（一种抗 TNF-α 的单克隆抗体）治疗。采集外周血，提取外周血单个核细胞。通过流式细胞术检测 T 细胞亚群及其 CIRs 的表达，即 T 细胞免疫受体含 Ig 和 ITIM 结构域（TIGIT）、淋巴细胞激活基因 3（LAG-3）、细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）、B 和 T 淋巴细胞相关蛋白（BTLA）、内皮蛋白 C 受体（PROCR）、足突蛋白（PDPN）、程序性细胞死亡 1（PD-1）和 T 细胞免疫球蛋白黏蛋白家族成员 3（TIM-3）的比例。
中重度斑块状银屑病患者外周血 Tregs 减少，英夫利昔单抗治疗后增加。外周血 CD4 T 细胞上 TIGIT、LAG-3 表达减少，PDPN 表达增加。英夫利昔单抗增强了循环 CD4 T 细胞上的 TIGIT、LAG-3、CTLA-4 表达，但降低了 PROCR 表达。值得注意的是，基线（治疗前）时循环 Tregs 的频率和 CD4 T 细胞上 TIGIT 的表达水平与英夫利昔单抗治疗后 PASI 评分降低的程度呈负相关。
抗 TNF-α 治疗增加了银屑病患者循环 CD4 T 细胞中 Tregs、TIGIT、LAG-3、CTLA-4 的表达，但降低了 PROCR 的表达。基线时循环 Tregs 的比例和循环 CD4 T 细胞上 TIGIT 的表达水平可能可作为预测英夫利昔单抗治疗后疾病缓解程度的标志物。
