title: Plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Clinical studies have identified that reduced numbers of circulating plasmacytoid dendritic cells (pDCs) act as a predictor of cardiovascular events in coronary artery disease and that pDCs are detectable in the shoulder region of human atherosclerotic plaques, where rupture is most likely to occur. Results from animal models are controversial, with pDCs seen to inhibit or promote lesion development depending on the experimental settings. Here, we investigated the role of pDCs in atherosclerosis in apolipoprotein E-deficient mice.
  
  
  RESULTS
  We demonstrated that the aorta and spleen of both apolipoprotein E-deficient and C57BL/6 mice displayed similar numbers of pDCs, with similar activation status. In contrast, assessment of antigen uptake/presentation using the Eα/Y-Ae system revealed that aortic pDCs in apolipoprotein E-deficient(-) mice were capable of presenting in vivo systemically administered antigen. Continuous treatment of apolipoprotein E-deficient mice with anti-mouse plasmacytoid dendritic cell antigen 1 (mPDCA-1) antibody caused specific depletion of pDCs in the aorta and spleen and significantly reduced atherosclerosis formation in the aortic sinus (by 46%; P<0.001). Depletion of pDCs also reduced macrophages (by 34%; P<0.05) and increased collagen content (by 41%; P<0.05) in aortic plaques, implying a more stable plaque phenotype. Additionally, pDC depletion reduced splenic T-cell activation and inhibited interleukin-12, chemokine (C-X-C motif) ligand 1, monokine induced by interferon-γ, interferon γ-induced protein 10, and vascular endothelium growth factor serum levels.
  
  
  CONCLUSIONS
  These results identify a critical role for pDCs in atherosclerosis and suggest a potential role for pDC targeting in the control of the pathology.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Macritchie
authors.forename: Gianluca
authors.initials: G
authors.lastname: Grassia
authors.forename: Suleman R
authors.initials: SR
authors.lastname: Sabir
authors.forename: Marcella
authors.initials: M
authors.lastname: Maddaluno
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Armando
authors.initials: A
authors.lastname: Ialenti
authors.forename: Mariola
authors.initials: M
authors.lastname: Kurowska-Stolarska
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.forename: Pasquale
authors.initials: P
authors.lastname: Maffia
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000276:immunology; D001011:Aorta / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005260:Female; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000906:Antibodies; D000954:Antigens, Surface; D001057:Apolipoproteins E; D018836:Inflammation Mediators