BackgroundNeutrophil extracellular trap (NET) formation has been described to be closely involved in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the effect of polydatin (PD) on NET formation and its effects on disease activity in lupus-prone mouse models.MethodsIn vitro, neutrophils from SLE patients and healthy people stimulated with phorbol 12-myristate 13-acetate (PMA) or phosphate-buffered saline (PBS) were treated with PD, and reactive oxygen species (ROS) production and NET formation examined. In vivo, pristane-induced lupus (PIL) mice were treated with vehicle, PD, mycophenolate mofetil (MMF) or cyclophosphamide (CYC) while MRL/lpr mice were treated with vehicle or PD. Proteinuria, serum autoantibodies, ROS production, NET formation and kidney histopathology were tested.ResultsConsistent with previous findings, blood neutrophils from SLE patients showed increased spontaneous NET formation. Both in vivo and in vitro, PD treatment significantly inhibited ROS production and NET release by neutrophils. In MRL/lpr mouse model, PD administration reduced the proteinuria, circulating autoantibody levels, and deposition of NETs and immune complex in the kidneys. In addition, PD treatment ameliorated lupus-like features in PIL mice as MMF or CYC did.ConclusionsPD treatment inhibited ROS-mediated NET formation and ameliorated lupus manifestations in both PIL mice and MRL/lpr mice. These results highlight the involvement of NETosis in SLE pathogenesis and reveal that PD might be a potential therapeutic agent for SLE or other autoimmune diseases.

Trafficking of dendritic cells (DCs) to lymph nodes (LNs) to present Ags is a crucial step in the pathogenesis of rheumatoid arthritis (RA). Matrix metalloproteinase-9 (MMP-9) is the key molecule for DC migration. Thus, blocking MMP-9 to inhibit DC migration may be a novel strategy to treat RA. In this study, we used anti-MMP-9 Ab to treat collagen-induced arthritis (CIA) in DBA/1J mice and demonstrated that anti-MMP-9 Ab treatment significantly suppressed the development of CIA via the modulation of DC trafficking. In anti-MMP-9 Ab-treated CIA mice, the number of DCs in draining LNs was obviously decreased. In vitro, anti-MMP-9 Ab and MMP-9 inhibitor restrained the migration of mature bone marrow-derived DCs in Matrigel in response to CCR7 ligand CCL21. In addition, blocking MMP-9 decreased T and B cell numbers in LNs of CIA mice but had no direct influence on the T cell response to collagen II by CD4 + T cells purified from LNs or spleen. Besides, anti-MMP-9 Ab did not impact on the expression of MHC class II, CD40, CD80, CD86, and chemokine receptors (CCR5 and CCR7) of DCs both in vivo and in vitro. Furthermore, we discovered the number of MMP-9 2/2 DCs trafficking from footpads to popliteal LNs was dramatically reduced as compared with wild type DCs in both MMP-9 2/2 mice and wild type mice. Taken together, these results indicated that DC-derived MMP-9 is the crucial factor for DC migration, and blocking MMP-9 to inhibit DC migration may constitute a novel strategy of future therapy for RA and other similar autoimmune diseases.