Cai Minchao, Zhou Tong, Wang Xuan, Shang Minghua, Zhang Yueyue, Luo Maocai, Xu Chundi, Yuan Weijie
Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University.
Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clin Exp Immunol. 2016 Mar;183(3):317-25. doi: 10.1111/cei.12723. Epub 2015 Nov 24.
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)-γ/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.
足细胞是免疫复合物的主要靶细胞,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黏附分子3结合非整合素分子(DC-SIGN)是一种具有免疫识别功能的天然免疫分子,参与细胞黏附及免疫调节的介导过程。在此,我们探究了DC-SIGN在足细胞上的表达及其在狼疮性肾炎(LN)免疫和炎症反应中的作用。在LN患者的肾小球中观察到DC-SIGN和免疫球蛋白(Ig)G1的表达。DC-SIGN与足细胞上的nephrin共表达。伴随LN小鼠蛋白尿增加,在20周龄时肾小球中观察到DC-SIGN和IgG1表达,至24周时肾功能恶化。抗DC-SIGN抗体处理的小鼠蛋白尿减少,肾功能缓解。体外使用LN小鼠血清刺激足细胞后,DC-SIGN、主要组织相容性复合体(MHC)II类分子和CD80的表达上调,T细胞增殖刺激增强,干扰素(IFN)-γ/白细胞介素(IL)-4比值升高。然而,抗DC-SIGN抗体处理可逆转这些情况。这些结果表明,LN中的足细胞可通过表达DC-SIGN发挥类似树突状细胞的功能,这可能参与肾组织的免疫和炎症反应。然而,阻断DC-SIGN可抑制足细胞的免疫功能,可能具有预防和治疗作用。