Programmed cell death-ligand 1 ameliorates psoriatic inflammation by inhibiting TCR-induced IL-17A production of T cells overexpressing PD-1

Abstract

Abstract Psoriasis is one of the most common chronic inflammatory diseases in the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death-1 (PD-1) is a co-inhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, it remains to be elucidated whether PD-1 is overexpressed on T cells in psoriasis and whether PD-1 agonist alleviates psoriatic inflammation. We examined PD-1 expression on IL-17A-producing T cells from Imiquimod (IMQ)-treated mice and psoriasis patients. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand-1-Fc (PD-L1-Fc) protein on IMQ-induced psoriatic inflammation. During IMQ-induced psoriatic inflammation, PD-1 is overexpressed on CD27−Vγ1− γδ T cells. Further, PD-1 expression on IL-17A+ T cells was confirmed in tissue samples from patients with psoriatic skin. In the CD27−Vγ1−γδ T cell population, Vγ4−γδ T cells with Vγ6 mRNA expression showed a high level of PD-1 expression. Further, these PD-1hiVγ4−(Vγ6+) γδ T cells were specialized for T-cell receptor (TCR)-induced IL-17A production, which was inhibited by PD-L1-Fc protein treatment. In IMQ-treated mice, PD-L1-Fc protein reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. In conclusion, PD-1 is overexpressed in IL-17A-producing T cells in both IMQ-treated mice and psoriasis patients, and recombinant PD-L1-Fc protein alleviates psoriatic inflammation in IMQ-treated mice.