title: Conventional dendritic cells at the crossroads between immunity and cholesterol homeostasis in atherosclerosis.
abstract: BACKGROUND
  Immunoinflammatory mechanisms are implicated in the atherogenic process. The polarization of the immune response and the nature of the immune cells involved, however, are major determinants of the net effect, which may be either proatherogenic or antiatherogenic. Dendritic cells (DCs) are central to the regulation of immunity, the polarization of the immune response, and the induction of tolerance to antigens. The potential role of DCs in atherosclerosis, however, remains to be defined.
  
  
  RESULTS
  We created a mouse model in which the lifespan and immunogenicity of conventional DCs are enhanced by specific overexpression of the antiapoptotic gene hBcl-2 under the control of the CD11c promoter. When studied in either low-density lipoprotein receptor-deficient or apolipoprotein E-deficient backgrounds, DC-hBcl2 mice exhibited an expanded DC population associated with enhanced T-cell activation, a T-helper 1 and T-helper 17 cytokine expression profile, and elevated production of T-helper 1-driven IgG2c autoantibodies directed against oxidation-specific epitopes. This proatherogenic signature, however, was not associated with acceleration of atherosclerotic plaque progression, because expansion of the DC population was unexpectedly associated with an atheroprotective decrease in plasma cholesterol levels. Conversely, depletion of DCs in hyperlipidemic CD11c-diphtheria toxin receptor/apolipoprotein E-deficient transgenic mice resulted in enhanced cholesterolemia, thereby arguing for a close relationship between the DC population and plasma cholesterol levels.
  
  
  CONCLUSIONS
  Considered together, the present data reveal that conventional DCs are central to the atherosclerotic process, because they are directly implicated in both cholesterol homeostasis and the immune response.
authors.affiliation: INSERM UMR-S U939, Hôpital de la Pitié, Paris, France.
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.forename: Thierry
authors.initials: T
authors.lastname: Huby
authors.forename: Flora
authors.initials: F
authors.lastname: Saint-Charles
authors.forename: Betty
authors.initials: B
authors.lastname: Ouzilleau
authors.forename: John
authors.initials: J
authors.lastname: Pirault
authors.forename: Virginie
authors.initials: V
authors.lastname: Deswaerte
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Miller
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D001323:Autoantibodies; D049109:Cell Proliferation; D002784:Cholesterol / Q000097:blood*; D016207:Cytokines; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D019254:Genes, bcl-2 / Q000235:genetics; D006706:Homeostasis; D007109:Immunity; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D002784:Cholesterol