Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
Department of Microbiology and Immunology, Northwestern University, 633 Clark St, Evanston, IL 60208, USA.
Int J Mol Sci. 2019 Sep 14;20(18):4566. doi: 10.3390/ijms20184566.
Natural killer T (NKT) cells are a distinct subset of lymphocytes that bridge the innate and adaptive immune response and can be divided into type I invariant NKT cells (iNKT) and type II NKT cells. The objective of this study is to examine the effects of NKT cell on lipid metabolism and the initiation and progression of atherosclerosis in LDL receptor deficient (LDLR) mice. Mice were fed an atherogenic diet for 4 or 8 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. The selective absence of iNKT cells in Jα18LDLR mice led to an increase in plasma cholesterol levels in female mice. Transgenic Vα14tg/LDLR mice with elevated numbers of iNKT cells had increased late atherosclerosis of the innominate artery, though absence of either iNKT cells or all NKT cells and other CD1d expressing cells had varying effects on atherosclerotic lesion burden in the ascending aortic arch and aortic root. These studies not only highlight the potential modulatory role played by NKT cells in atherosclerosis and lipid metabolism, but also raise the possibility that divergent roles may be played by iNKT and CD1d restricted cells such as type II NKT cells or other CD1d expressing cells.
自然杀伤 T (NKT) 细胞是淋巴细胞的一个独特亚群，连接先天免疫和适应性免疫反应，可分为 I 型不变自然杀伤 T (iNKT) 细胞和 II 型 NKT 细胞。本研究旨在探讨 NKT 细胞对 LDL 受体缺陷 (LDLR) 小鼠脂质代谢和动脉粥样硬化发生发展的影响。用致动脉粥样硬化饮食喂养小鼠 4 或 8 周，检测血浆脂质、脂蛋白和动脉粥样硬化情况。Jα18LDLR 小鼠中 iNKT 细胞的选择性缺失导致雌性小鼠血浆胆固醇水平升高。具有升高数量 iNKT 细胞的转基因 Vα14tg/LDLR 小鼠无名动脉晚期动脉粥样硬化增加，尽管缺失 iNKT 细胞或所有 NKT 细胞和其他表达 CD1d 的细胞对升主动脉弓和主动脉根部的动脉粥样硬化病变负担有不同的影响。这些研究不仅强调了 NKT 细胞在动脉粥样硬化和脂质代谢中可能发挥的调节作用，还提出了 iNKT 和 CD1d 限制细胞（如 II 型 NKT 细胞或其他表达 CD1d 的细胞）可能发挥不同作用的可能性。
