| BackgroundSystemic lupus erythematosus(SLE)is one of the most common autoimmune diseases which involves multiple systems and organs,and lupus nephritis(LN)is the most common complication.The pathogenesis of SLE is very complex.Studies have shown that genetic,immune disorders,hormones,infection and physicochemical environment are closely related to the occurrence and development of SLE and LN.Based on one of the characteristics of SLE,a variety of autoantibodies,which are mainly ANA and anti ds-DNA antibodies are produced and all types of LN have immune complex deposits.So T and B lymphocytes cell involved in adaptive immune response were first noticed and elucidated in the pathogenesis of SLE.However,there are few studies on innate immune response such as NK cell.Natural killer cell(NK)are the main cells in the innate immune response,and can regulate T and B lymphocytes in adaptive immune response by cell-cell interaction and secretion of a variety of cytokines and chemokines.So NK cells are considered to be the bridge between innate immune response and adaptive immune response.More and more studies have shown that NK cell are associated with organ specific autoimmune diseases.According to the theory of "licensing" proposed by Yokoyama,NK cells can be divided into two subsets: licensed and unlicensed NK cell.Studies have found that "unlicensed" NK cells can promote allograft cell survival in vivo during the acute rejection phase of bone marrow transplantation.The aim of this study is to investigate the role of unlicensed NK cell in the pathogenesis of lupus mice induced by Pristane ObjectiveTo explore the role of the "unlicensed" NK cell subsets in the pathogenesis of SLE and LN,and to provide a new idea for pathogenesis of SLE by inducing lupus mice model with Pristane.Methods1.Establishment of lupus mice model with Pristane:18 female,SPF BALB/c mice at age 9-10 weeks were randomly classified into 2 groups:(1)induction group(9 mice): intraperitoneal injection of 0.5ml Pristane.(2)control group(9 mice):intraperitoneal injection of 0.5 ml PBS.The experimental observation time was 7months.And the indexes included appearance,weight,urinary protein,autoantibody(ANA,anti ds-DNA antibody,anti nRNP/Sm antibody and anti ss-DNA antibody)level,kidney pathology(light microscopy and immunofluorescence).To compare the differences between the two groups.2.To investigate the relationship between unlicensed NK subsets and the pathogenesis of lupus mice by Pristane.27 female,SPF BALB/c mice at age 9-10 weeks were randomly classified into 3 groups:(1)"U-NK" group:9mice,Intraperitoneal injection of anti Ly49G2+ monoclonal antibody 4D11 was injected before the experiment;(2)"non-NK" group:9 mice,Anti-asialoGM1 was injected intraperitoneally before the experiment;(3)"Model" group: 9 mice.On the day of experiment,all of mices were injection 0.5ml Pristane.The observation time was 7 months,and observation indexes are: appearance,weight,urinary protein,autoantibody(ANA,anti ds-DNA antibody,anti nRNP/Sm antibody and anti ss-DNA antibody)level,kidney pathology(light microscopy and immunofluorescence)and flow cytometry detected the number ofNK cell.Results1.Some mice showed erythema and hair removal such as lupus in induced group,and urinary protein is +1~+2,four autoantibodies(ANA,anti ds-DNA antibody,anti nRNP/Sm antibody and anti ss-DNA antibody)appeared in serum.Renal pathology showed partial glomerular volume increased,mesangial cells and endothelial cell proliferation,renal interstitial infiltration of inflammatory cells with immunofluorescence under light microscope.Immunofluorescence indicated that IgG and IgM along the glomerular capillary loop deposition and mesangial area.2.After the end of experimental,there was no difference in survival and appearance between the 3 groups.The urinary protein,autoantibody levels and pathological changes of kidney in the U-NK group were significantly improved compared with the "non-NK" group and "model" group.Compared with the "model" group,the level of anti nRNP/Sm antibody and anti ss-DNA antibody and the fluorescence intensity of IgG and IgM in "non-NK" group were increased,so the situation was poor.The number of unlicensed NK cells in "U-NK" group was higher than that in "model" group detected by flow cytometry.ConclusionsPristane can induce female BALB/c mice to develop lupus models Unlicensed NK cells can inhibit the occurrence and development of SLE and lupus nephritis,and provide a new idea for the pathogenesis of SLE. |
