title: DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis.
abstract: 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.
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University.
authors.forename: Minchao
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University.
authors.forename: Minghua
authors.initials: M
authors.lastname: Shang
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University.
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Maocai
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chundi
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University.
authors.forename: Weijie
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000503:physiopathology; D037181:Lectins, C-Type / Q000235:genetics* / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D010641:Phenotype; D050199:Podocytes / Q000276:immunology* / Q000378:metabolism; D011507:Proteinuria; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: DC-SIGN; immunoregulation; lupus nephritis; podocytes