title: Mannose-binding lectin blunts macrophage polarization and ameliorates lupus nephritis.
abstract: BACKGROUND
  Deficiency in clearance of self nuclear antigens, including DNA, is the hallmark of systemic lupus erythematosus (SLE), a chronic autoimmnue disease characterized by the production of various autoantibodies, immune complex deposition and severe organ damage. Our previous studies revealed that administration of syngeneic BALB/c mice with activated lymphocyte-derived DNA (ALD-DNA) could induce SLE disease. Mannose-binding lectin (MBL), a secreted pattern recognition receptor with binding activity to DNA, has been proved to be a modulator of inflammation, but whether MBL takes responsibility for DNA clearance, modulates the DNA-mediated immune responses, and is involved in the development of DNA-induced SLE disease remain poorly understood.
  
  
  RESULTS
  The levels of serum MBL significantly decreased in lupus mice induced by ALD-DNA and were negatively correlated with SLE disease. MBL blunted macrophage M2b polarization by inhibiting the MAPK and NF-κB signaling while enhancing the activation of CREB. Furthermore, MBL suppressed the ability of ALD-DNA-stimulated macrophages to polarize T cells toward Th1 cells and Th17 cells. Importantly, MBL supplement in vivo could ameliorate lupus nephritis.
  
  
  CONCLUSIONS
  These results suggest MBL supplement could alleviate SLE disease and might imply a potential therapeutic strategy for DNA-induced SLE, which would further our understanding of the protective role of MBL in SLE disease.
authors.affiliation: Department of Immunology and Institute for Immunobiology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Cai
authors.forename: Weijuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D037601:Mannose-Binding Lectin; D016328:NF-kappa B; D004247:DNA; D020928:Mitogen-Activated Protein Kinases