The expression of mCTLA-4 in skin lesion inversely correlates with the severity of psoriasis

Abstract

Background: Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and increased T cell infiltration. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key factor that affects T cell function and immune response. However, whether the expression of CTLA-4 affects the severity of psoriasis is still unknown.

Objective: The aim of the project was to investigate the correlation between the expression of CTLA-4 and the severity of psoriasis.

Methods: The plasma soluble CTLA-4 levels and membrane CTLA-4 expression were measured by enzyme-linked immunosorbent assay and immunohistochemistry analysis in mild, moderate and severe psoriasis patients, respectively. Imiquimod-induced mouse model of psoriasis was treated with CTLA-4 immunoglobulin fusion protein (CTLA-4 Ig) or anti-CTLA-4 antibody. Epidermal thickness and infiltrating CD3+ T cell counts were evaluated.

Results: The plasma soluble CTLA-4 levels had no significant difference among mild, moderate, and severe patients (p > 0.05). However, the membrane CTLA-4 expression in skin was significantly higher in mild psoriasis patients compared to moderate and severe psoriasis patients (17652.86 ± 18095.66 vs 6901.36 ± 4400.77 vs 3970.24 ± 5509.15, p < 0.001). Furthermore, in imiquimod-induced mouse model of psoriasis, the results showed that mimicking CTLA-4 function improved the skin phenotype and reduced epidermal thickness (172.87 ± 28.25 vs 245.87 ± 36.61 μm, n = 6, p < 0.01) as well as infiltrating CD3+ T cell counts (5.09 ± 3.45 vs 13.45 ± 4.70, p < 0.01) compared to control group. However, blocking CTLA-4 function aggregated the skin phenotype including enhanced epidermal thickness and infiltrating CD3+ T cell counts compared to control group.

Conclusion: These results indicated that the expression of mCTLA-4 in skin lesion inversely correlated with the severity of psoriasis and CTLA-4 might play a critical role in the disease severity of psoriasis.

Keywords: CTLA-4; Mouse model of psoriasis; Psoriasis; T cells.