Ox-LDL-induced CD80<SUP>+</SUP> macrophages expand pro-atherosclerotic NKT cells via CD1d in atherosclerotic mice and hyperlipidemic patients

作者全名：Wang, Yin; Zou, Yao; Jiang, Qingsong; Li, Wenming; Chai, Xinyu; Zhao, Tingrui; Liu, Siyi; Yuan, Zhiyi; Yu, Chao; Wang, Tingting

作者地址：[Wang, Yin; Jiang, Qingsong; Chai, Xinyu; Liu, Siyi; Yuan, Zhiyi; Yu, Chao; Wang, Tingting] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Wang, Yin; Jiang, Qingsong; Chai, Xinyu; Liu, Siyi; Yuan, Zhiyi; Yu, Chao; Wang, Tingting] Chongqing Key Lab Pharmaceut Metab Res, Chongqing, Peoples R China; [Wang, Yin; Chai, Xinyu; Liu, Siyi; Yuan, Zhiyi; Yu, Chao; Wang, Tingting] Chongqing Pharmacodynam Evaluat Engn Technol Res C, Chongqing, Peoples R China; [Zou, Yao] Peoples Hosp Chongqing Liangjiang New Dist, Dept Pharm, Chongqing, Peoples R China; [Jiang, Qingsong] Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing, Peoples R China; [Li, Wenming] Chongqing Med Univ, Univ Town Hosp, Dept Clin Lab, Chongqing, Peoples R China; [Zhao, Tingrui] Third Hosp Mianyang, Sichuan Mental Hlth Ctr, Dept Clin Pharm, Mianyang, Sichuan, Peoples R China

通信作者：Yu, C; Wang, TT (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China.; Yu, C; Wang, TT (通讯作者)，Chongqing Key Lab Pharmaceut Metab Res, Chongqing, Peoples R China.; Yu, C; Wang, TT (通讯作者)，Chongqing Pharmacodynam Evaluat Engn Technol Res C, Chongqing, Peoples R China.

来源：AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001251972600002

JCR分区：Q1

影响因子：5

年份：2024

卷号：326

期号：6

开始页：C1563

结束页：C1572

文献类型：Article

关键词：atherosclerosis; CD1d; CD80+macrophages; interferon-gamma; natural killer T cells

摘要：Atherosclerosis is an inflammatory disease of blood vessels involving the immune system. Natural killer T (NKT) cells, as crucial components of the innate and acquired immune systems, play critical roles in the development of atherosclerosis. However, the mechanism and clinical relevance of NKT cells in early atherosclerosis are largely unclear. The study investigated the mechanism influencing NKT cell function in apoE deficiency-induced early atherosclerosis. Our findings demonstrated that there were higher populations of NKT cells and interferon-gamma (IFN-gamma)-producing NKT cells in the peripheral blood of patients with hyperlipidemia and in the aorta, blood, spleen, and bone marrow of early atherosclerotic mice compared with the control groups. Moreover, we discovered that the infiltration of CD80(+) macrophages and CD1d expression on CD80(+) macrophages in atherosclerotic mice climbed remarkably. CD1d expression increased in CD80(+) macrophages stimulated by oxidized low-density lipoprotein (ox-LDL) ex vivo and in vitro. Ex vivo coculture of macrophages with NKT cells revealed that ox-LDL-induced CD80+ macrophages presented lipid antigen alpha-Galcer (alpha-galactosylceramide) to NKT cells via CD1d, enabling NKT cells to express more IFN-gamma. Furthermore, a greater proportion of CD1d+ monocytes and CD1d(+)CD80(+) monocytes were found in peripheral blood of hyperlipidemic patients compared with that of healthy donors. Positive correlations were found between CD1d+CD80+ monocytes and NKT cells or IFN-gamma(+) NKT cells in hyperlipidemic patients. Our findings illustrated that CD80+ macrophages stimulated NKT cells to secrete IFN-gamma via CD1d-presenting alpha-Galcer, which may accelerate the progression of early atherosclerosis. Inhibiting lipid antigen presentation by CD80+ macrophages to NKT cells may be a promising immune target for the treatment of early atherosclerosis.

基金机构：Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202200470]

基金资助正文：This work was supported by The Science and Technology Research Program of Chongqing Municipal Education Commission Grant No. KJQN202200470 (to T. Wang).