Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
Front Immunol. 2019 Aug 7;10:1865. doi: 10.3389/fimmu.2019.01865. eCollection 2019.
Psoriasis is a chronic immune-mediated inflammatory skin disease, with over-activated interleukin (IL)-17-producing CD4 T cells (Th17) and repressed regulatory T (Treg) cells. IL-21 is a Th17-related cytokine and plays an important role in the pathogenesis of psoriasis. However, the mechanism by which IL-21 affects the pathogenic progress of psoriasis remains poorly understood. IL-21 and IL-21 receptor (IL-21R) expression in normal and psoriatic lesional skin were determined by immumohistochemical staining, immunofluorescence staining, and western blotting. The levels of IL-21, IL-17A, and IL-22 in the culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-10 in the culture supernatants was measured by cytometric bead array (CBA). The mRNA expression levels were assessed by quantitative polymerase chain reaction (qPCR). CD4 T cells were isolated from the peripheral blood mononuclear cells (PBMCs) from the psoriasis patients and healthy individuals and then treated with or without IL-21 for 3 days. The proportions of Th17 and Treg cells were determined by flow cytometric analysis. IL-21 and IL-21R were highly expressed in the lesional skin and peripheral blood of psoriasis patients. IL-21 promoted CD4 T cells proliferation and Th17 cells differentiation and inhibiting Treg cells differentiation by upregulating RORγt expression and downregulating Foxp3 expression, with increased expression and secretion of IL-17A and IL-22. The proportion of Treg cells was negatively correlated with that of Th17 cells in psoriasis patients. Our results suggest that IL-21 may promote psoriatic inflammation by inducing imbalance in Th17 and Treg cell populations.
银屑病是一种慢性免疫介导的炎症性皮肤病，其特征是过度激活产生白细胞介素 (IL)-17 的 CD4 T 细胞（Th17）和抑制调节性 T（Treg）细胞。IL-21 是一种与 Th17 相关的细胞因子，在银屑病的发病机制中发挥重要作用。然而，IL-21 影响银屑病发病进程的机制仍知之甚少。通过免疫组织化学染色、免疫荧光染色和 Western blot 检测正常和银屑病皮损皮肤中 IL-21 和 IL-21 受体（IL-21R）的表达。通过酶联免疫吸附试验（ELISA）测量培养上清液中 IL-21、IL-17A 和 IL-22 的水平。通过流式细胞术分析测定培养上清液中 IL-10 的水平。通过定量聚合酶链反应（qPCR）评估 mRNA 表达水平。从银屑病患者和健康个体的外周血单个核细胞（PBMC）中分离 CD4 T 细胞，然后用或不用 IL-21 处理 3 天。通过流式细胞术分析测定 Th17 和 Treg 细胞的比例。IL-21 和 IL-21R 在银屑病患者的皮损皮肤和外周血中高表达。IL-21 通过上调 RORγt 表达和下调 Foxp3 表达促进 CD4 T 细胞增殖和 Th17 细胞分化，并抑制 Treg 细胞分化，导致 IL-17A 和 IL-22 的表达和分泌增加。银屑病患者中 Treg 细胞的比例与 Th17 细胞的比例呈负相关。我们的研究结果表明，IL-21 可能通过诱导 Th17 和 Treg 细胞群体失衡来促进银屑病炎症。
