CD200 / CD200R Signaling Pathway Investigate The Pathogenesis Of Systemic Lupus Erythematosus

BackgroundThe pathagenesis mechanism of Systemic lupus erythematosus may include malfuncton of T cells, B cells and dendritic cells. The imbalance of immune tolerance and excess releasing of inflmatory cytokine lead to abnormal activation of B cells and production of autoimmune antigens. T regulatory cells are proliferation anergic and they can negatively regulate T cell reproduction through contact inhibition. The numeric and functonal defects of Treg have been considered as the critical factor of SLE pathagenisis. CD200is a type I membrane glycoprotein which is expressed on a number of cell types. The ligaton of CD200R can regulate the activation threshold of inflammatory immune responses, prevention of graft rejection, and maintain the immune homeostasis. Previous studies have shown CD200/CD200R regulating the function of macrophage and mast cells, and focused on animal models such as collagen induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE). The knowledge of CD200/CD200R axis in human especially in SLE patients was very limited and lack of report. In the previous study of our lab, CD200mRNA and CD200R mRNA decreased in SLE patients, yet the percentage of cells in PBMC expressing CD200increased, indicating an abnormality in CD200signal.In this research we try to investigate the possible effect of CD200signal on the proportion of Treg cells and on the producton of interleukin10(IL-10).MethodPBMC from SLE patients and health controls were cocultured with CD200Fc、CD200R1Fc and anti-CD200R1separately for48hours. Intracellular staining was processed and flow cytometry detection was analyzed to determine the change of Treg. The concentration of IL-10in the supernatant was measured by ELISA.Results1. The CD4+CD25highFoxp3+T cells in Newly unset activate SLE patients were lower than health control (0.902±1.026%vs.1.95±1.306%, P=0.014), while the CD4+CD25-Foxp3+T cells in SLE patients were higher than health control (6.37±4.63%vs.1.82±1.21%, P=0.001)2. The CD200Fc has little effect on the CD4+CD25highFoxp3+and CD4+CD25"Foxp3+T cells in health controls. But in SLE patients, CD200Fc could reduce the percentage of CD4+CD25highFoxp3+T (0.661±0.702%vs.0.951±1.035%,p=0.036)3. IL-10levels in PBMC culture supernatant were elevated in SLE patients, which can be damatic reduced by coculture with anti-CD200R1antibodies.ConclusionThe percentage of CD25high Treg was decreased in SLE patient while the percentege of CD4+CD25-Foxp3+T cells was increased. when cocultured with CD200-Fc the CD25high Treg in SLE patients was reduced. SLE patient had higher IL-10in PBMC culture supernatant which decreased significantly by anti-CD200R1antibodies. CD200/CD200R1axis may exert effect in SLE pathogenesis through Treg and cytokine production.