Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy

Abstract

Psoriasis is a common immune-mediated, chronic inflammatory genetic-related disease that affects patients' quality of life. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of progenitor and immature myeloid cells which are expanded in psoriatic skin lesions and peripheral blood. However, the role of MDSCs in the pathogenesis of psoriasis remains unclear. Here, we confirmed that the accumulation of human MDSCs is remarkably increased in skin lesions of psoriasis patients by flow cytometry. Depleting MDSCs by Gemcitabine significantly suppresses IMQ-induced psoriatic inflammation and epidermal thickening as well as Th17 and Treg cell accumulation. Moreover, through the RNA-Seq technique, we validated some differentially expressed genes on CD4⁺ T-cells of IMQ-induced-MDSC-depleted mice such as IL-21 and Timd2, which are involved in Th17-cell differentiation or T-cell activation. Interestingly, neutralizing IL-21R by antibody reduces IMQ-induced epidermal thickening through downregulating the infiltration of MDSCs and Th17 cells. Our data suggest that targeting myeloid-derived suppressor cells is a novel strategy for antipsoriasis therapy. IL-21 may be a potential therapeutic target in psoriasis.