Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
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靶向骨髓源性抑制细胞是抗银屑病治疗的新策略
DOI：
10.1155/2020/8567320
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发表时间：
2020-06-28
影响因子：
4.6
通讯作者：
Peng, Cong
中科院分区：
文献类型：
--
作者：
Chen, Chao;Tan, Lirong;Peng, Cong
银屑病是一种常见的免疫调节的慢性炎症性遗传相关疾病，影响患者的生活质量。髓系抑制细胞(MDSCs)是一类异质性的祖细胞和幼稚髓系细胞，在银屑病皮损和外周血中扩增。然而，MDSCs在银屑病发病机制中的作用尚不清楚。在此，我们通过流式细胞术证实，银屑病患者皮损中人MDSCs的积聚显著增加。吉西他滨耗尽MDSCs可显著抑制ImQ诱导的银屑病炎症和表皮增厚，以及Th17和Treg细胞积聚。此外，通过RNA-Seq技术，我们验证了在ImQ诱导的MDSC耗竭小鼠的CD4+T细胞上差异表达的基因，如IL-21和Timd2，它们参与了Th17细胞的分化或T细胞的激活。有趣的是，抗体中和IL-21R通过下调MDSCs和Th17细胞的渗透来减少ImQ诱导的表皮增厚。我们的数据表明，靶向髓系来源的抑制细胞是治疗银屑病的一种新策略。IL-21可能是治疗银屑病的潜在靶点。
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.