| BackgroundCD200is a glycoprotein widely expressed on lymphocytes, neurocytes as well as epithelial cells, while CD200R is restrictedly expressed on myeloid cells such as dendritic cells and macrophages. CD200/CD200R axis plays a crucial immunoregulatory role in inflammation, allergy and graft versus host disease by CD200-CD200R interaction.Systemic lupus Erythematous(SLE) is a chronic, multisystem-involved typical autoimmune disease which related to abnormally activated T cells,B cells and deficiency in clearance of apoptotic cells. Dendritic cells acting as antigen presenting cells also contribute to the pathogenesis of SLE.The expression and effect of CD200R on dendritic cells in SLE are less known. In this research, we tried to analyze the expression of CD200R on different subsets of dendritic cells and its correlation with clinical manifestation. Studied CD200/CD200R axis function through monocytes derived dendritic cells, and tried to speculate its role in the pathogenesis in SLE.MethodTwenty patients diagnosed of SLE were recuited. Seventeen sex and age matched health volunteers were accepted as health controls (HC). Anti-coagulated peripheral blood was collected and mononuclear cells were isolated.CD200R expression on dendritic cells was determined by flow cytometry.Monocytes derived dendritic cells (MoDC) were obtained from culture of CD14+monocytes which were separated by CD14micro beads with GM-CSF and IL-4. MoDCs were stimulated by LPS.Analysis of CD200R and matured markers such as HLA-DR, CD83, CD86expression on MoDCs from different treated groups (culture media, LPS, LPS+CD200) were realized by flow cytometry. IL-6and IL-10level were detected by ELISA.Proliferation of CD4+lymphocytes in mixed lymphocytes reaction was detected by flow cytometry by labled with CFSE.Results1. SLE patients had lower percentage of plasmacytoid dendritic cells (0.50±0.08%vs.1.59±0.31%, p=0.002) and relatively higher percentage of monocytes in peripheral blood mononuclear cells (PBMC)(18.66±2.77%vs.10.52±1.04%, p=0.014).2. CD200R was lower expressed on plasmacytoid dendritic cells and myeloid dendritic cells in SLE (mDC:20.51±2.87%vs.27.95±2.00%, p=0.046; pDC:47.97±5.50%vs.65.14±4.72%, p=0.027).3. The level of CD200R expression on myeloid dendritic cells was negatively correlated with ESR in SLE (r=-0.552, R2=0.3043, p=0.041).4. The amount of PBMC was decreased in SLE, while the differentiation rate of monocytes to MoDCs was increased in SLE (SLE vs. HC:30.10±5.75%vs.16.90±4.03%, p=0.043).5. LPS induced CD200R down regulation on MoDCs both in HC and SLE (HC LPS vs. M:CD200R+%53.54±4.74%vs.62.09±5.18%, p<0.001; MFI41.18±2.28vs.45.50±2.93, p=0.002; MFI×CD200R+%22.53±2.78vs.28.97±3.58, p<0.001. SLE LPS vs. M:CD200R+%45.10±7.53%vs.52.33±8.18%, p=0.023; MFI38.79±1.88vs.43.28±2.37, p=0.015; MFI×CD200R+%18.01±3.64vs.23.37±4.49, p<0.001).6. LPS stimulated MoDCs to express higher HLA-DR, CD83, CD86, with more secretion of IL-6and IL-10. Matured MoDCs were more potent to stimulate CD4+lymphocytes to proliferate in allogeneic MLR (p<0.05).7. CD200could promote the function of LPS in HC, causing more active and matured state of MoDCs (LPS+CD200vs. LPS:HLA-DR+%77.45±7.59%vs.75.59±8.22%, p=0.038; CD83+%×MFI14.41±2.71vs.12.15±2.96, p=0.003; CD86+%×MFI254.78±56.77vs.228.40±53.95, p=0.009; IL-6:297.57±52.86pg/ml/104vs.255.04±41.80pg/ml/104, p=0.032; IL-10:24.91±6.03pg/ml/104vs.28.29±6.72pg/ml/104, p=0.024), while not in SLE patients (p>0.05).8. MoDCs treated with LPS and CD200of HC were more potent to stimulate CD4+lymphotes to proliferate in MLR than SLE (15.2±2.6%vs.8.8±1.5%, p=0.049). ConclusionThe amount of dendritic cells was decreased in SLE, accompany with lower expression of CD200R. This was negatively correlated with ESR in mDC. CD200could enhance the the function of LPS which could induce MoDC matured, causing MoDC more immunostimulatoy to some extent in healthy controls, while this was not observed in SLE. |
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