Targeting myeloid-derived suppressor cells is a novel strategy for anti-psoriasis therapy

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 cells accumulation. Moreover, through the RNA-Seq technique, we validated some differentially expressed genes on CD4+ T cells of IMQ-induced-MDSCs-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 down-regulating the infiltration of MDSCs and Th17 cells. Our data suggest that targeting myeloid-derived suppressor cells is a novel strategy for anti-psoriasis therapy. IL-21 may be a potential therapeutic target in psoriasis.

银屑病是一种常见的免疫介导、慢性炎症性遗传相关性疾病，严重影响患者的生活质量。髓系来源抑制细胞（Myeloid-derived suppressor cells, MDSCs）是一类异质性的祖细胞与未成熟髓系细胞群体，在银屑病皮损与外周血中出现扩增。然而，MDSCs在银屑病发病机制中的作用仍不明确。本研究通过流式细胞术证实，银屑病患者皮损中人类MDSCs的蓄积水平显著升高。采用吉西他滨（Gemcitabine）耗竭MDSCs，可显著抑制咪喹莫特（IMQ）诱导的银屑病样炎症与表皮增厚，同时减少Th17细胞与调节性T（Treg）细胞的蓄积。此外，本研究借助RNA测序（RNA-Seq）技术，验证了咪喹莫特诱导的MDSCs耗竭小鼠的CD4+ T细胞中的部分差异表达基因，如参与Th17细胞分化或T细胞活化的IL-21与Timd2。有趣的是，通过抗体中和IL-21受体（IL-21R），可通过下调MDSCs与Th17细胞的浸润，减轻咪喹莫特诱导的表皮增厚。本研究数据表明，靶向髓系来源抑制细胞是一种新型的抗银屑病治疗策略，IL-21或可成为银屑病的潜在治疗靶点。