title: Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice.
abstract: Lipopolysaccharide (LPS) has been shown to accelerate atherosclerosis and to increase the prevalence of IL-4-producing natural killer T (NKT) cells in various tissues. However, the role of NKT cells in the development of LPS-induced atherosclerotic lesions has not been fully tested in NKT cell-deficient mice. Here, we examined the lesion development in apolipoprotein E knockout (apoE-KO) mice and apoE-KO mice on an NKT cell-deficient, CD1d knockout (CD1d-KO) background (apoE-CD1d double knockout; DKO). LPS (0.5 μg/g body weight/wk) or phosphate-buffered saline (PBS) was intraperitoneally administered to apoE-KO and DKO mice (8-wk old) for 5 wk and atherosclerotic lesion areas were quantified thereafter. Consistent with prior reports, NKT cell-deficient DKO mice showed milder atherosclerotic lesions than apoE-KO mice. Notably, LPS administration significantly increased the lesion size in apoE-KO, but not in DKO mice, compared to PBS controls. Our findings suggest that LPS, and possibly LPS-producing bacteria, aggravate the development of atherosclerosis primarily through NKT cell activation and subsequent collaboration with NK cells.
authors.affiliation: Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Andoh
authors.forename: Hisako
authors.initials: H
authors.lastname: Ogura
authors.forename: Masashi
authors.initials: M
authors.lastname: Satoh
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimano
authors.forename: Hironori
authors.initials: H
authors.lastname: Okuno
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishimori
authors.forename: Koji
authors.initials: K
authors.lastname: Eshima
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tamauchi
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Otani
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Nakai
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Kazunori
authors.initials: K
authors.lastname: Onoé
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000276:immunology*; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D055610:Antigens, CD1d; D001057:Apolipoproteins E; C526879:Cd1d1 protein, mouse; D008070:Lipopolysaccharides