Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA.
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
J Invest Dermatol. 2016 Apr;136(4):798-808. doi: 10.1016/j.jid.2015.12.036. Epub 2016 Jan 22.
The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis. Despite psoriasis being a hyperinflammatory condition, Mo-MDSCs were elevated in psoriatic patient peripheral blood mononuclear cells compared to nonpsoriatic healthy controls (2.6% vs. 0.9%, P < 0.002). Freshly isolated psoriatic Mo-MDSCs directly suppressed CD8 T-cell proliferation less efficiently than healthy control Mo-MDSCs. In addition, psoriatic Mo-MDSCs expressed reduced surface expression of programmed cell death protein 1 compared to healthy controls. Additional in vitro assays also demonstrated that psoriatic and control Mo-MDSCs both induce regulatory T-cell conversion from naïve T effector cells, but, importantly, the regulatory T cells induced by psoriatic Mo-MDSCs displayed decreased suppressive functionality. These results suggest that aberrations in psoriatic Mo-MDSCs prevent proper suppression of effector T-cell expansion and hamper the immune system's ability to correctly self-regulate.
银屑病病理学的临床程度部分受到免疫网络缺陷的调节，包括调节性 T 细胞抑制作用的缺陷。最近，已经表明 CD14(+) HLA-DR(-/low)单核细胞髓系来源的抑制性细胞（Mo-MDSCs）通过其抑制机制之一抑制 T 细胞活化。然而，对于 Mo-MDSCs 的作用及其与 T 细胞抑制的功能关系在涉及人类慢性免疫介导的炎症性疾病，包括银屑病方面知之甚少。尽管银屑病是一种炎症过度的疾病，但与非银屑病健康对照组相比，银屑病患者外周血单核细胞中的 Mo-MDSCs 升高（2.6%对 0.9%，P<0.002）。与健康对照组 Mo-MDSCs 相比，新鲜分离的银屑病 Mo-MDSCs 直接抑制 CD8 T 细胞增殖的效率较低。此外，与健康对照组相比，银屑病 Mo-MDSCs 表达的程序性细胞死亡蛋白 1 表面表达降低。额外的体外测定还表明，银屑病和对照 Mo-MDSCs 均可诱导幼稚 T 效应细胞向调节性 T 细胞的转化，但重要的是，由银屑病 Mo-MDSCs 诱导的调节性 T 细胞显示出降低的抑制功能。这些结果表明，银屑病 Mo-MDSCs 的异常导致效应 T 细胞扩增的适当抑制受阻，并阻碍免疫系统正确的自我调节能力。
