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.

中文翻译：

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靶向髓样抑制细胞是一种抗牛皮癣治疗的新策略。

牛皮癣是一种常见的免疫介导的，慢性炎症性遗传相关疾病，会影响患者的生活质量。骨髓来源的抑制细胞（MDSC）是祖细胞和未成熟髓细胞的异质群体，它们在银屑病皮肤损伤和外周血中扩增。然而，MDSCs在牛皮癣发病机理中的作用仍不清楚。在这里，我们证实通过流式细胞术在牛皮癣患者的皮肤病变中人类MDSCs的积累显着增加。吉西他滨消耗MDSC可以显着抑制IMQ诱导的牛皮癣炎症和表皮增厚以及Th17和Treg细胞积聚。此外，通过RNA-Seq技术，我们验证了CD4 ⁺上的一些差异表达基因IMQ诱导的MDSC耗竭小鼠的T细胞（如IL-21和Timd2）参与Th17细胞分化或T细胞活化。有趣的是，通过下调MDSCs和Th17细胞的浸润，抗体中和IL-21R可以减少IMQ诱导的表皮增厚。我们的数据表明靶向髓样抑制细胞是抗牛皮癣治疗的一种新策略。IL-21可能是牛皮癣的潜在治疗靶标。