Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice

The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial...

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Autores principales:	Yoshinori Ohmura, Naoki Ishimori, Akimichi Saito, Takashi Yokota, Shunpei Horii, Satoshi Tokuhara, Kazuya Iwabuchi, Hiroyuki Tsutsui
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	α-galactosylceramide apolipoprotein E knockout mice atherosclerosis brachiocephalic artery macrophages matrix metalloproteinase Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c8ee207cfeff4968be24b348cb4471a8
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spelling	oai:doaj.org-article:c8ee207cfeff4968be24b348cb4471a82021-11-25T17:56:47ZNatural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice10.3390/ijms2222124511422-00671661-6596https://doaj.org/article/c8ee207cfeff4968be24b348cb4471a82021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12451https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial role in atherogenesis. However, it remained unclear whether iNKT cells are also involved in plaque instability. Apolipoprotein E (apoE) knockout mice were fed a standard diet (SD) or a high-fat diet (HFD) for 8 weeks. Moreover, the SD- and the HFD-fed mice were divided into two groups according to the intraperitoneal injection of α-galactosylceramide (αGC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE/Jα18 double knockout mice, which lack iNKT cells, were also fed an SD or HFD. Plaque instability was assessed at the brachiocephalic artery by the histological analysis. In the HFD group, αGC significantly enhanced iNKT cell infiltration and exacerbated atherosclerotic plaque instability, whereas the depletion of iNKT cells attenuated plaque instability compared to PBS-treated mice. Real-time PCR analyses in the aortic tissues showed that αGC administration significantly increased expressional levels of inflammatory genes such as IFN-γ and MMP-2, while the depletion of iNKT cells attenuated these expression levels compared to those in the PBS-treated mice. Our findings suggested that iNKT cells are involved in the exacerbation of plaque instability via the activation of inflammatory cells and upregulation of MMP-2 in the vascular tissues.Yoshinori OhmuraNaoki IshimoriAkimichi SaitoTakashi YokotaShunpei HoriiSatoshi TokuharaKazuya IwabuchiHiroyuki TsutsuiMDPI AGarticleα-galactosylceramideapolipoprotein E knockout miceatherosclerosisbrachiocephalic arterymacrophagesmatrix metalloproteinaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12451, p 12451 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	α-galactosylceramide apolipoprotein E knockout mice atherosclerosis brachiocephalic artery macrophages matrix metalloproteinase Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	α-galactosylceramide apolipoprotein E knockout mice atherosclerosis brachiocephalic artery macrophages matrix metalloproteinase Biology (General) QH301-705.5 Chemistry QD1-999 Yoshinori Ohmura Naoki Ishimori Akimichi Saito Takashi Yokota Shunpei Horii Satoshi Tokuhara Kazuya Iwabuchi Hiroyuki Tsutsui Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
description	The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial role in atherogenesis. However, it remained unclear whether iNKT cells are also involved in plaque instability. Apolipoprotein E (apoE) knockout mice were fed a standard diet (SD) or a high-fat diet (HFD) for 8 weeks. Moreover, the SD- and the HFD-fed mice were divided into two groups according to the intraperitoneal injection of α-galactosylceramide (αGC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE/Jα18 double knockout mice, which lack iNKT cells, were also fed an SD or HFD. Plaque instability was assessed at the brachiocephalic artery by the histological analysis. In the HFD group, αGC significantly enhanced iNKT cell infiltration and exacerbated atherosclerotic plaque instability, whereas the depletion of iNKT cells attenuated plaque instability compared to PBS-treated mice. Real-time PCR analyses in the aortic tissues showed that αGC administration significantly increased expressional levels of inflammatory genes such as IFN-γ and MMP-2, while the depletion of iNKT cells attenuated these expression levels compared to those in the PBS-treated mice. Our findings suggested that iNKT cells are involved in the exacerbation of plaque instability via the activation of inflammatory cells and upregulation of MMP-2 in the vascular tissues.
format	article
author	Yoshinori Ohmura Naoki Ishimori Akimichi Saito Takashi Yokota Shunpei Horii Satoshi Tokuhara Kazuya Iwabuchi Hiroyuki Tsutsui
author_facet	Yoshinori Ohmura Naoki Ishimori Akimichi Saito Takashi Yokota Shunpei Horii Satoshi Tokuhara Kazuya Iwabuchi Hiroyuki Tsutsui
author_sort	Yoshinori Ohmura
title	Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
title_short	Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
title_full	Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
title_fullStr	Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
title_full_unstemmed	Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
title_sort	natural killer t cells are involved in atherosclerotic plaque instability in apolipoprotein-e knockout mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c8ee207cfeff4968be24b348cb4471a8
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Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice

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