title: Natural killer T cells accelerate atherogenesis in mice.
abstract: We have investigated the potential role of CD1d-restricted natural killer T (NKT) cells in the development of atherosclerosis in mice. When fed an atherogenic diet (AD), NKT cell-deficient CD1d(-/-) mice had significantly smaller atherosclerotic lesions than AD-fed C57BL/6 (wild-type [WT]) mice. A significant reduction in atherosclerotic lesions was also demonstrated in AD-fed, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice reconstituted with CD1d(-/-) bone marrow cells compared with the lesions observed in Ldlr(-/-)mice reconstituted with WT marrow cells. In addition, repeated injections of alpha-GalCer or the related glycolipid OCH to apolipoprotein E knockout (apoE(-/-)) mice during the early phase of atherosclerosis significantly enlarged the lesion areas compared with mice injected with vehicle control. However, administering alpha-GalCer to apoE(-/-) mice with established lesions did not significantly increase the lesion area but considerably decreased the collagen content. Atherosclerosis development in either AD-fed WT or apoE(-/-) mice was associated with the presence of Valpha14Jalpha18 transcripts in the atherosclerotic arterial walls, indicating that NKT cells were recruited to these lesions. Thioglycolate-elicited macrophages pulsed with oxidized low-density lipoproteins expressed enhanced CD1d levels and induced NKT cells to produce interferon-gamma, a potentially proatherogenic T-helper 1 (TH1) cytokine. Collectively, we conclude that NKT cells are proatherogenic in mice.
authors.affiliation: Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Nakai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishimori
authors.forename: Nyambayar
authors.initials: N
authors.lastname: Dashtsoodol
authors.forename: Keiko
authors.initials: K
authors.lastname: Watano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mishima
authors.forename: Chikako
authors.initials: C
authors.lastname: Iwabuchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Jelena S
authors.initials: JS
authors.lastname: Bezbradica
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Kazunori
authors.initials: K
authors.lastname: Onoé
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis; D055610:Antigens, CD1d; D001057:Apolipoproteins E / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology*; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D004036:Diet, Atherogenic; D005434:Flow Cytometry; D006017:Glycolipids / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D019076:Transgenes
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D001057:Apolipoproteins E; D006017:Glycolipids; D012333:RNA, Messenger; D007371:Interferon-gamma