Journal Article

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

Iwabuchi, Kazuya, Horii, Shunpei, Tsutsui, Hiroyuki, Tokuhara, Satoshi, Saito, Akimichi, Ohmura, Yoshinori, Yokota, Takashi, Ishimori, Naoki

2021

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Antigens / Apolipoproteins / Atherosclerosis / Atherosclerosis - etiology / Atherosclerosis - genetics / Atherosclerosis - immunology / Atherosclerosis - pathology / Brachial Artery - immunology / Brachial Artery - pathology / Cell Movement - drug effects / Collagen / Cytokines / Diet, High-Fat - adverse effects / Fatty acids / Galactosylceramides - pharmacology / Gene expression / Gene Expression Regulation / Inflammation / Interferon-gamma - genetics / Interferon-gamma - immunology / Killer Cells, Natural - drug effects / Killer Cells, Natural - immunology / Killer Cells, Natural - pathology / Lymphocyte Activation / Lymphocytes / Macrophages - drug effects / Macrophages - immunology / Macrophages - pathology / Male / Matrix Metalloproteinase 2 - genetics / Matrix Metalloproteinase 2 - immunology / Mice / Mice, Inbred C57BL / Mice, Knockout, ApoE / Pathophysiology / Plaque, Atherosclerotic - etiology / Plaque, Atherosclerotic - genetics / Plaque, Atherosclerotic - immunology / Plaque, Atherosclerotic - pathology / Rodents / T cell receptors / Veins & arteries