Abstract
Abnormal expression of CD200/CD200R1 may contribute to the immunologic abnormalities in patients with systemic lupus erythematosus (SLE). This study aimed to assess the function of CD200/CD200R1and impact of CD200-Fc on dendritic cells in lupus-prone NZB/WF1 mice. Female NZB/WF1 mice were treated with CD200-Fc or control for 4 weeks. Plasma samples were collected to measure autoantibody levels. The expression levels of CD200/CD200R1 in peripheral blood mononuclear cells (PBMCs) and splenocytes were examined. The percentage of CD200/CD200R1-positive cells in splenocytes from NZB/WF1 mice was lower than that of C57BL/6 mice (p < 0.05). The plasma level of anti-dsDNA was significantly higher in NZB/WF1 mice than C57BL/6 mice (p < 0.001). However, the anti-dsDNA levels decreased (p = 0.047) after CD200-Fc treatment. Finally, CD200-Fc reduced the levels of IL-6 (p = 0.017) and IL-10 (p = 0.03) in the dendritic cell culture supernatant. This study suggests that the immunosuppressive CD200/CD200R1 signaling pathway might be involved in the immunopathology of NZB/WF1 mice; the present results merit further exploration of agents that can modulate the CD200/CD200FR1 pathway as a therapy for human lupus.
Highlights
Abnormal expression of CD200/CD200R1 may contribute to the immunologic abnormalities in patients with systemic lupus erythematosus (SLE)
Our previous study demonstrated that the expression of CD200 and CD200R1 is higher and lower, respectively, in dendritic cells (DCs), including both Plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs), in patients with SLE compared with healthy controls, which may contribute to immunologic abnormalities and can be corrected by CD200-Fc treatment through reducing DC migration in patients with SLE16
Our findings demonstrated that the OD450 value for anti-dsDNA was significantly higher in the NZB/WF1 group compared with the C57BL/6 group (0.62 ± 0.10 vs. 0.29 ± 0.06, p < 0.001), while there was no significant difference between the levels of anti-nuclear antibody (ANA) and anti-nRNP/Sm (0.69 ± 0.11 vs. 0.60 ± 0.12, p > 0.05 and 0.43 ± 0.05 vs. 0.47 ± 0.09, p > 0.05, respectively) between these two groups
Summary
Abnormal expression of CD200/CD200R1 may contribute to the immunologic abnormalities in patients with systemic lupus erythematosus (SLE). This study aimed to assess the function of CD200/ CD200R1and impact of CD200-Fc on dendritic cells in lupus-prone NZB/WF1 mice. Insufficient clearance of apoptotic material by dendritic cells (DCs), which leads to the release of modified autoantigens that can initiate an immune response, has been thought to play a pivotal role in the immunopathogenesis of SLE3. Phagocytosis of apoptotic material leads to the maturation of myeloid dendritic cells (mDCs) and production of proinflammatory cytokines, including IL-66. Our previous study demonstrated that the expression of CD200 and CD200R1 is higher and lower, respectively, in DCs, including both pDCs and mDCs, in patients with SLE compared with healthy controls, which may contribute to immunologic abnormalities and can be corrected by CD200-Fc treatment through reducing DC migration in patients with SLE16.
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