摘  要

一、背景

银屑病是一种常见的慢性复发性炎症性皮肤疾病，T细胞起关键作用，发病机制与IL23/Th17 轴异常活化有关，但上游机制尚未被完全阐明。TIGIT与CD226在维持免疫系统稳态中具有重要作用，参与多种自身免疫性疾病的发生发展。表达TIGIT的调节性T（regulatory T cells，Treg）细胞可显著抑制辅助性T （helper T cells，Th）细胞Th1/Th17的促炎反应。虽然有研究表明银屑病患者外周血中CD4⁺T细胞上TIGIT表达水平降低，但对于银屑病患者皮损及外周血中TIGIT与CD226表达情况目前尚无深入研究。

二、目的：

对银屑病患者皮损及外周血中TIGIT、CD226表达进行比较性研究，探讨其与银屑病发病机制间的关系，进一步丰富对银屑病免疫学发病机制的理解。

三、方法

利用公共数据库获得公开的普通转录组测序（bulk RNA sequencing，bulk RNA-Seq）及单细胞转录组测序（single-cell RNA-sequencing，scRNA-Seq）数据，对普通转录组（GSE121212）和单细胞转录组（GSE151177）数据进行分析。招募寻常型银屑病患者和健康受试者各17名，采集外周血并分离人外周血单个核细胞（peripheral blood mononuclear cells ，PBMC），对TIGIT、CD226及T细胞表面标志物CD4、CD8免疫荧光染色，流式细胞术分析TIGIT、CD226在CD4⁺T细胞、CD8⁺T细胞的表达情况。

四、结果

通过转录组数据分析发现，银屑病皮损TIGIT与CD226表达水平相较对照组升高，并在scRNA-Seq数据中发现TIGIT与CD226主要在CD4⁺T细胞和CD8⁺T细胞上表达。研究还发现，外周血淋巴细胞中CD4⁺T细胞上CD226表达比例较健康对照组显著降低（34.66% vs 43.67%，P值=0.045），TIGIT⁺CD226^-CD8⁺T细胞亚群比例也显著降低（9.90% vs 14.84%，P值=0.033）。但TIGIT、CD226在外周血中的表达水平与银屑病面积和严重程度指数（psoriasis area and severity index，PASI）评分之间无明显相关性。

五、结论

银屑病皮损转录组中TIGIT、CD226表达升高，主要表达在CD4⁺T细胞和CD8⁺T细胞上。银屑病患者外周血中CD4⁺T细胞上CD226表达比例降低，且TIGIT⁺CD226^-CD8⁺T细胞亚群比例也较健康对照组降低。

Abstract

Background: Psoriasis is a common chronic recurrent inflammatory skin disease in which T cells play an important role in pathogenesis. The abnormal activation of the IL23/Th17 axis is associated with the pathogenesis of psoriasis, but the upstream mechanism has not been fully elucidated. TIGIT and CD226 play an important role in maintaining the immune system's homeostasis and are involved in the development of various autoimmune diseases. The expression of TIGIT on regulatory T cells can significantly inhibit the pro-inflammatory response of Th1/Th17. Although it has been found that the expression level of TIGIT on CD4⁺T cells in the peripheral blood of psoriasis patients is decreased, there is currently no in-depth research on the expression of TIGIT and CD226 in the skin lesions and peripheral blood of psoriasis patients.

Objective: A comparative study on the expression of TIGIT and CD226 in psoriasis patients' skin lesions and peripheral blood, to explore the potential relationship between them and the pathogenesis of psoriasis, and to further enrich the understanding of the immunopathogenesis of psoriasis.

Methods: Using publicly available databases, we obtained both bulk RNA-Seq and scRNA-Seq data from ordinary transcriptional profiling (GSE121212) and single-cell transcriptional profiling (GSE151177) for analysis. We recruited 17 patients with common psoriasis and 17 healthy controls, collected peripheral blood, and isolated human PBMC from them. We performed immunofluorescence staining with antibodies against TIGIT, CD226, and T-cell surface markers such as CD4 and CD8, and analyzed the expression of these markers in CD4⁺ T cells and CD8⁺ T cells using flow cytometry.

Results: By analyzing the transcriptome data, it was found that the expression levels of TIGIT and CD226 in psoriasis lesions were higher than those in the control group, and TIGIT and CD226 were found to be primarily expressed on CD4⁺T cells and CD8⁺T cells through scRNA-Seq analysis. The study also revealed that the proportion of CD226 expression on CD4⁺T cells in the peripheral blood of psoriasis patients was significantly lower than that in healthy controls (34.66% vs 43.67%, P value = 0.045), and the proportion of TIGIT⁺CD226^-CD8⁺T cell subgroups was also significantly lower (9.90% vs 14.84%, P value = 0.033). However, the expression levels of TIGIT and CD226 in the peripheral blood were not significantly correlated with the PASI scores.

Conclusion: In psoriasis lesions, the expression levels of TIGIT and CD226 are elevated at the transcriptional level, primarily expressed on CD4⁺T cells and CD8⁺T cells.  In the peripheral blood of psoriasis patients, the proportion of CD226 expression on CD4⁺T cells is significantly lower than that in healthy controls, and the proportion of TIGIT⁺CD226^-CD8⁺T cell subgroups is also significantly lower compared to the healthy controls.