title: CD1d-dependent activation of NKT cells aggravates atherosclerosis.
abstract: Adaptive and innate immunity have been implicated in the pathogenesis of atherosclerosis. Given their abundance in the lesion, lipids might be targets of the atherosclerosis-associated immune response. Natural killer T (NKT) cells can recognize lipid antigens presented by CD1 molecules. We have explored the role of CD1d-restricted NKT cells in atherosclerosis by using apolipoprotein E-deficient (apoE-/-) mice, a hypercholesterolemic mouse model that develops atherosclerosis. ApoE-/- mice crossed with CD1d-/- (CD1d-/-apoE-/-) mice exhibited a 25% decrease in lesion size compared with apoE-/- mice. Administration of alpha-galactosylceramide, a synthetic glycolipid that activates NKT cells via CD1d, induced a 50% increase in lesion size in apoE-/- mice, whereas it did not affect lesion size in apoE-/-CD1d-/- mice. Treatment was accompanied by an early burst of cytokines (IFNgamma, MCP-1, TNFalpha, IL-2, IL-4, IL-5, and IL-6) followed by sustained increases in IFNgamma and IL-4 transcripts in the spleen and aorta. Early activation of both T and B cells was followed by recruitment of T and NKT cells to the aorta and activation of inflammatory genes. These results show that activation of CD1d-restricted NKT cells exacerbates atherosclerosis.
authors.affiliation: Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tupin
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
authors.forename: Rima
authors.initials: R
authors.lastname: Elhage
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
authors.forename: Hans-Gustaf
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.forename: Gabrielle Paulsson
authors.initials: GP
authors.lastname: Berne
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D001057:Apolipoproteins E