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DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis

机译:DC-SIGN在足细胞上的表达及其在狼疮性肾炎炎症免疫反应中的作用

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Podocytes, the main target of immune complex, participate actively in the development of glomerular injury as immune cells. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate immune molecular that has an immune recognition function, and is involved in mediation of cell adhesion and immunoregulation. Here we explored the expression of DC-SIGN on podocytes and its role in immune and inflammatory responses in lupus nephritis (LN). Expression of DC-SIGN and immunoglobulin (Ig)G1 was observed in glomeruli of LN patients. DC-SIGN was co-expressed with nephrin on podocytes. Accompanied by increased proteinuria of LN mice, DC-SIGN and IgG1 expressions were observed in the glomeruli from 20 weeks, and the renal function deteriorated up to 24 weeks. Mice with anti-DC-SIGN antibody showed reduced proteinuria and remission of renal function. After the podocytes were stimulated by serum of LN mice in vitro, the expression of DC-SIGN, major histocompatibility complex (MHC) class II and CD80 was up-regulated, stimulation of T cell proliferation was enhanced and the interferon (IFN)-/interleukin (IL)-4 ratio increased. However, anti-DC-SIGN antibody treatment reversed these events. These results suggested that podocytes in LN can exert DC-like function through their expression of DC-SIGN, which may be involved in immune and inflammatory responses of renal tissues. However, blockage of DC-SIGN can inhibit immune functions of podocytes, which may have preventive and therapeutic effects.
机译:足细胞是免疫复合物的主要靶标,它作为免疫细胞积极参与肾小球损伤的发展。树突状细胞特异性细胞间粘附分子3-捕获非整联蛋白(DC-SIGN)是一种先天免疫分子,具有免疫识别功能,并参与细胞粘附和免疫调节的介导。在这里,我们探讨了DC-SIGN在足细胞上的表达及其在狼疮性肾炎(LN)的免疫和炎症反应中的作用。 LN患者肾小球中观察到DC-SIGN和免疫球蛋白(Ig)G1的表达。 DC-SIGN与肾素在足细胞上共表达。随着LN小鼠蛋白尿的增加,从20周开始观察到肾小球的DC-SIGN和IgG1表达,并且肾功能在长达24周时恶化。带有抗DC-SIGN抗体的小鼠表现出蛋白尿减少和肾功能缓解。 LN小鼠血清体外刺激足细胞后,DC-SIGN,II类主要组织相容性复合体(MHC)和CD80的表达上调,T细胞增殖刺激增强,干扰素(IFN)-/白介素(IL)-4比例增加。但是,抗DC-SIGN抗体治疗可以逆转这些事件。这些结果表明,LN中的足细胞可通过表达DC-SIGN发挥DC样功能,这可能与肾脏组织的免疫和炎症反应有关。然而,DC-SIGN的阻断可以抑制足细胞的免疫功能,这可能具有预防和治疗作用。

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