Natural killer T cells accelerate atherogenesis in mice
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 sig...
Main Authors: | , , , , , , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
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American Society of Hematology
2004
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author | Nakai, Y Iwabuchi, K Fujii, S Ishimori, N Dashtsoodol, N Watano, K Mishima, T Iwabuchi, C Tanaka, S Bezbradica, J Nakayama, T Taniguchi, M Miyake, S Yamamura, T Kitabatake, A Joyce, S Van Kaer, L Onoé, K |
author_facet | Nakai, Y Iwabuchi, K Fujii, S Ishimori, N Dashtsoodol, N Watano, K Mishima, T Iwabuchi, C Tanaka, S Bezbradica, J Nakayama, T Taniguchi, M Miyake, S Yamamura, T Kitabatake, A Joyce, S Van Kaer, L Onoé, K |
author_sort | Nakai, Y |
collection | OXFORD |
description | 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 α-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 α-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 Vα14Jα18 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-γ, a potentially proatherogenic T-helper 1 (TH1) cytokine. Collectively, we conclude that NKT cells are proatherogenic in mice. |
first_indexed | 2024-03-06T19:53:57Z |
format | Journal article |
id | oxford-uuid:24e61328-a2e9-444d-934c-222eb11d710d |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T19:53:57Z |
publishDate | 2004 |
publisher | American Society of Hematology |
record_format | dspace |
spelling | oxford-uuid:24e61328-a2e9-444d-934c-222eb11d710d2022-03-26T11:52:46ZNatural killer T cells accelerate atherogenesis in miceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:24e61328-a2e9-444d-934c-222eb11d710dEnglishSymplectic Elements at OxfordAmerican Society of Hematology2004Nakai, YIwabuchi, KFujii, SIshimori, NDashtsoodol, NWatano, KMishima, TIwabuchi, CTanaka, SBezbradica, JNakayama, TTaniguchi, MMiyake, SYamamura, TKitabatake, AJoyce, SVan Kaer, LOnoé, KWe 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 α-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 α-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 Vα14Jα18 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-γ, a potentially proatherogenic T-helper 1 (TH1) cytokine. Collectively, we conclude that NKT cells are proatherogenic in mice. |
spellingShingle | Nakai, Y Iwabuchi, K Fujii, S Ishimori, N Dashtsoodol, N Watano, K Mishima, T Iwabuchi, C Tanaka, S Bezbradica, J Nakayama, T Taniguchi, M Miyake, S Yamamura, T Kitabatake, A Joyce, S Van Kaer, L Onoé, K Natural killer T cells accelerate atherogenesis in mice |
title | Natural killer T cells accelerate atherogenesis in mice |
title_full | Natural killer T cells accelerate atherogenesis in mice |
title_fullStr | Natural killer T cells accelerate atherogenesis in mice |
title_full_unstemmed | Natural killer T cells accelerate atherogenesis in mice |
title_short | Natural killer T cells accelerate atherogenesis in mice |
title_sort | natural killer t cells accelerate atherogenesis in mice |
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