Infliximab modifies regulatory T cells and co-inhibitory receptor expression on circulating T cells in psoriasis

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Biomarker; Co-inhibitory receptors; Infliximab; Psoriasis; Regulatory T cells.