Cao Lauren Y, Chung Jin-Sung, Teshima Takahiro, Feigenbaum Lawrence, Cruz Ponciano D, Jacobe Heidi T, Chong Benjamin F, Ariizumi Kiyoshi
Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
J Invest Dermatol. 2016 Sep;136(9):1801-1810. doi: 10.1016/j.jid.2016.02.816. Epub 2016 May 25.
Psoriasis vulgaris is an inflammatory skin disease caused by hyperactivated T cells regulated by positive and negative mechanisms; although the former have been much studied, the latter have not. We studied the regulatory mechanism mediated by myeloid-derived suppressor cells (MDSCs) and showed that MDSCs expanded in melanoma patients express dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand, a critical mediator of T-cell suppressor function. We examined expansion of DC-HIL(+) MDSCs in psoriasis and characterized their functional properties. Frequency of DC-HIL(+) monocytic MDSCs (CD14(+)HLA-DR(no/low)) in blood and skin was markedly increased in psoriatic patients versus healthy control subjects, but there was no statistically significant relationship with disease severity (based on Psoriasis Area and Severity Index score). Blood DC-HIL(+) MDSC levels in untreated patients were significantly higher than in treated patients. Compared with melanoma-derived MDSCs, psoriatic MDSCs exhibited significantly reduced suppressor function and were less dependent on DC-HIL, but they were capable of inhibiting proliferation and IFN-γ and IL-17 responses of autologous T cells. Psoriatic MDSCs were functionally diverse among patients in their ability to suppress allogeneic T cells and in the use of either IL-17/arginase I or IFN-γ/inducible nitric oxide synthase axis as suppressor mechanisms. Thus, DC-HIL(+) MDSCs are expanded in psoriasis patients, and their mechanistic heterogeneity and relative functional deficiency may contribute to the development of psoriasis.
寻常型银屑病是一种由正负机制调节的T细胞过度活化引起的炎症性皮肤病；尽管对前者已进行了大量研究，但后者尚未得到充分研究。我们研究了髓系来源的抑制性细胞（MDSCs）介导的调节机制，并表明在黑色素瘤患者中扩增的MDSCs表达树突状细胞相关硫酸乙酰肝素蛋白聚糖依赖性整合素配体，这是T细胞抑制功能的关键介质。我们检测了银屑病中DC-HIL(+) MDSCs的扩增情况，并对其功能特性进行了表征。与健康对照受试者相比，银屑病患者血液和皮肤中DC-HIL(+)单核细胞MDSCs（CD14(+)HLA-DR(无/低)）的频率显著增加，但与疾病严重程度（基于银屑病面积和严重程度指数评分）无统计学显著关系。未经治疗的患者血液中DC-HIL(+) MDSC水平显著高于接受治疗的患者。与黑色素瘤来源的MDSCs相比，银屑病MDSCs的抑制功能显著降低，对DC-HIL的依赖性较小，但它们能够抑制自体T细胞的增殖以及IFN-γ和IL-17反应。银屑病MDSCs在抑制同种异体T细胞的能力以及使用IL-17/精氨酸酶I或IFN-γ/诱导型一氧化氮合酶轴作为抑制机制方面，患者之间存在功能差异。因此，DC-HIL(+) MDSCs在银屑病患者中扩增，其机制的异质性和相对功能缺陷可能有助于银屑病的发展。
