Expression of Co‐Inhibitory Molecules on Lymphocytes of Patients With Psoriasis

ABSTRACT This study aimed to investigate the prevalence of co‐inhibitory molecules (CIMs) on lymphocytes in patients with psoriasis (PsO). Combining bioinformatics analysis and experimental validation, we first analyzed the GSE109248 dataset to characterize lymphocyte immunoinfiltration patterns and CIM‐related gene expression profiles in PsO patients compared with healthy donors (HDs). Subsequently, peripheral blood mononuclear cells (PBMCs) from 15 PsO patients and 8 HDs were systematically examined to quantify surface expression levels of TIGIT/CD226, PD‐1, LAG‐3, and TIM‐3 across various T cell subpopulations and NK cells, thereby complementing the transcriptomic findings with functional cellular insights. The Results show that no notable differences were observed in the levels of NK cells, CD4 + , and CD8 + T cells when comparing PsOs to HDs in the GEO dataset and clinical samples. However, blood samples indicated a significant rise in CD4 + and CD8 + effector memory T cells (TEM) in PsOs compared to HDs ( p < 0.05). Further examination showed an increase in the proportion of TIGIT + CD8 + TEMs ( p < 0.05), while that of TIM‐3 + CD4 + TEMs exhibited a decrease ( p < 0.05). The percentages of CD4 + and CD8 + TEM cells expressing CD226 were significantly elevated in PsOs compared to HDs (both p < 0.01), whereas those expressing CD62L were significantly diminished (both p < 0.001). Additionally, the ratio of PD‐1 + NK was increased ( p < 0.05). Subgroup analysis between various degrees of disease severity in PsO patients showed that compared with those with mild psoriasis, patients with moderate to severe psoriasis had a decrease in the ratio of TEM in CD4+ and CD8+ T cells (both p < 0.05), an increase in percentage and MIF of TEM with CD62L expression in CD4 + T cells (both p < 0.05), a higher MIF of TIM‐3 expression on CD8 + T cells ( p < 0.01) and a higher MIF of PD‐1 on NK cells ( p < 0.05). The differential expression of TIGIT/CD226 on CD8 + TEM could indicate ongoing activation of lymphocytes. The extremely decreased expression of CD62L + TEM cells may indicate a significant shedding of CD62L from immune cells, which may suggest a release of lymphocytes into serum and aggravate systemic inflammation of PsO. However, the PD‐1 expression model on NK cells may necessitate additional research within a larger population for its significance in psoriasis. The relatively small sample size (15 PsO patients and 8 healthy donors) may limit the statistical power and generalizability of the findings; thus, larger cohorts are warranted to confirm these results.