Cross-talk between iNKT cells and monocytes triggers an atheroprotective immune response in SLE patients with asymptomatic plaque
Cross-talk between iNKT cells and monocytes triggers an atheroprotective immune response in SLE patients with asymptomatic plaque
复制标题
DOI：
10.1126/sciimmunol.aah4081
复制
发表时间：
2016-12-01
影响因子：
24.8
通讯作者：
Jury, Elizabeth C.
中科院分区：
文献类型：
--
作者：
Smith, Edward;Croca, Sara;Jury, Elizabeth C.
加速性动脉粥样硬化是自身免疫性风湿性疾病系统性红斑狼疮（SLE）的并发症。我们质疑不变的自然杀伤T（iNKT）细胞在这一过程中所发挥的作用，因为它们不仅在自身免疫中有缺陷，而且在CD 1d介导的脂质抗原呈递反应中促进动脉粥样硬化。与无斑块的SLE患者相比，来自无症状斑块的SLE患者（SLE-P）的iNKT细胞增殖和白细胞介素-4产生增加。抗炎iNKT细胞表型与血脂异常相关，并由单核细胞磷脂表达改变和iNKT细胞与单核细胞而非B细胞之间的CD 1d介导的串扰驱动。健康iNKT细胞在健康单核细胞和SLE-P血清存在下分化，使巨噬细胞向抗炎M2表型极化。相反，临床心血管疾病患者的iNKT细胞无反应，促炎单核细胞增加。iNKT细胞功能可以将SLE患者的免疫应答、脂质和心血管疾病联系起来，并与血清脂质分类学一起帮助预测SLE患者的临床前动脉粥样硬化。
Accelerated atherosclerosis is a complication of the autoimmune rheumatic disease systemic lupus erythematosus (SLE). We questioned the role played by invariant natural killer T (iNKT) cells in this process because they not only are defective in autoimmunity but also promote atherosclerosis in response to CD1d-mediated lipid antigen presentation. iNKT cells from SLE patients with asymptomatic plaque (SLE-P) had increased proliferation and interleukin-4 production compared with those from SLE patients with no plaque. The anti-inflammatory iNKT cell phenotype was associated with dyslipidemia and was driven by altered monocyte phospholipid expression and CD1d-mediated cross-talk between iNKT cells and monocytes but not B cells. Healthy iNKT cells differentiated in the presence of healthy monocytes and SLE-P serum polarized macrophages toward an anti-inflammatory M2 phenotype. Conversely, patients with clinical cardiovascular disease had unresponsive iNKT cells and increased proinflammatory monocytes. iNKT cell function could link immune responses, lipids, and cardiovascular disease in SLE patients and, together with serum lipid taxonomy, help predict preclinical atherosclerosis in SLE patients.