DC-SIGN expression on podocytes and its role in immune and inflammatory responses of lupus nephritis / 中华肾脏病杂志

ABSTRACT

Objective To explore the expression of DC?SIGN, the phenotype of dendritic cells (DCs), on podocytes, and its role in immune and inflammatory responses of lupus nephritis (LN). Methods DC?SIGN and IgG1 expression in renal tissues of lupus nephritis patients were observed by immunohistochemistry and immunofluorescence. The 4?week old LN mice were randomly divided into the experimental group and the intervention group. C57BL/6J mice were used as normal control group. Mice of the intervention group were injected anti?DC?SIGN antibody at 6?week old. Mice were sacrificed at 16, 20, 24, 28?week old respectively, to observe the mice renal function and pathological changes. And DC?SIGN and IgG1 expression in renal tissue were observed by immunohistochemistry and immunofluorescence. In addition, mice podocytes were treated with serum of LN mice. Flow cytometry was used to investigate the expression of MHC II, CD80 and DC?SIGN expression on podocytes. Mixed lymphocyte reaction was used to detect the ability of stimulating T cells proliferation. IFN?gamma and IL?4 in supernatant were determined by ELISA. Results (1) Expression of DC?SIGN and IgG1 was found in glomeruli of lupus nephritis patients. (2) Accompanied by increased proteinuria of LN mice from 20?week old (P<0.01), DC?SIGN and IgG1 expression was found in glomeruli, and the renal function deteriorated up to 24 week?old (P<0.01). Mice with anti?DC?SIGN antibody intervention appeared reduced proteinuria and remission of renal function (P<0.01). (3) After stimulated by serum of LN mice, the expression of DC?SIGN, MHC II and CD80 was up?regulated, stimulation of T cell proliferation was enhanced (P<0.01), and IFN?gamma/IL?4 ratio increased (P<0.01). Anti?DC?SIGN antibody treatment down?regulated the expressions of DC?SIGN, MHC II and CD80 on podocytes, decreased the ability of stimulating T cell proliferation and lowered the ratio of IFN?gamma/IL?4 (P<0.01). Conclusions Podocytes in lupus nephritis can play DC?like function through the expression of DC?SIGN, which may be involved in immune and inflammatory responses of renal tissue. However, inhibiton of DC?SIGN can depress immune function of podocytes and have prevention and treatment effect.