title: The inhibitory FcγRIIb modulates the inflammatory response and influences atherosclerosis in male apoE(-/-) mice.
abstract: BACKGROUND
  Atherosclerosis is widely accepted as an inflammatory disease involving both innate and adaptive immunity. B cells and/or antibodies have previously been shown to play a protective role against atherosclerosis. Aside from their ability to bind to antigens, antibodies can influence inflammatory responses by interacting with various Fcγ receptors on the surface of antigen presenting cells. Although studies in mice have determined that stimulatory Fcγ receptors contribute to atherosclerosis, the role of the inhibitory Fcγ receptor IIb (FcγRIIb) has only recently been investigated.
  
  
  RESULTS
  To determine the importance of FcγRIIb in modulating the adaptive immune response to hyperlipidemia, we generated FcγRIIb-deficient mice on the apoE-deficient background (apoE/FcγRIIb(-/-)). We report that male apoE/FcγRIIb(-/-) mice develop exacerbated atherosclerosis that is independent of lipid levels, and is characterized by increased antibody titers to modified LDL and pro-inflammatory cytokines in the aorta.
  
  
  CONCLUSIONS
  These findings suggest that antibodies against atherosclerosis-associated antigens partially protect against atherosclerosis in male apoE(-/-) mice by conveying inhibitory signals through the FcγRIIb that downregulate pro-inflammatory signaling via other immune receptors. These data are the first to describe a significant in vivo effect for FcγRIIb in modulating the cytokine response in the aorta in male apoE(-/-) mice.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, USA. yanice.mendez@vanderbilt.edu
authors.forename: Yanice V
authors.initials: YV
authors.lastname: Mendez-Fernandez
authors.forename: Bonnie G
authors.initials: BG
authors.lastname: Stevenson
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Diehl
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Braun
authors.forename: Nekeithia S
authors.initials: NS
authors.lastname: Wade
authors.forename: Roman
authors.initials: R
authors.lastname: Covarrubias
authors.forename: Sander
authors.initials: S
authors.lastname: van Leuven
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Amy S
authors.initials: AS
authors.lastname: Major
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology; D000941:Antigens / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007249:Inflammation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000235:genetics* / Q000502:physiology*
chemical_list: D000941:Antigens; D001057:Apolipoproteins E; D016207:Cytokines; C499172:Fcgr2b protein, mouse; D008077:Lipoproteins, LDL; D017452:Receptors, IgG