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

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.