Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(-/-) Mice.
Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(-/-) Mice.
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磷酸胆碱引发的树突状细胞会加剧 ApoE(-/-) 小鼠动脉粥样硬化的发展。
DOI：
10.1253/circrep.cr-20-0118
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发表时间：
2021-01-16
期刊：
影响因子：
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通讯作者：
Yu KW
中科院分区：
文献类型：
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作者：
Dong Q;Yu J;Ding Y;Ji QW;Zhu RR;Wei YZ;Xu WB;Zhong YC;Zhu ZF;Meng K;Peng YD;Sun HT;Wang Y;Pan CL;Zeng QT;Yu KW
工作背景：动脉粥样硬化是一种炎症性疾病，涉及对抗原（包括氧化低密度脂蛋白（oxLDL）和磷酸胆碱（PC））的适应性和先天性免疫应答的激活。树突状细胞（Dendritic cells，DC）是激活T细胞的抗原呈递细胞，存在于动脉粥样硬化病变中并在免疫器官中被激活。然而，PC促进动脉粥样硬化的机制尚不清楚。方法 和 结果：为了评估PC是否通过DC促进动脉粥样硬化，将2×105个经PC-锁孔血蓝蛋白激活的DC（DC +PC-KLH）注射到Apoe-/-小鼠体内，并确定斑块的特征以及DC对细胞和体液免疫的影响针对PC-KLH。注射DC +PC-KLH的小鼠的动脉粥样硬化病变明显大于对照组，病变中的炎症增加，斑块不稳定。此外，在骨髓来源的DC和幼稚T细胞共培养后，使用流式细胞术表征DC +PC-KLH。DC +PC-KLH表现出炎性表型，CD 86、CD 40和主要组织相容性复合物II类分子（MHC-II）增加，促进PC特异性辅助性T细胞（Th）1和Th 17细胞在体内和体外分化。此外，向小鼠给予DC +PC-KLH 2周后，这些小鼠产生了PC和oxLDL特异性IgG 2a，而对照组则不产生。结论：这些结果表明，DC提呈PC促进对PC的特异性免疫，增加病变炎症反应，加速动脉粥样硬化，这可能解释了PC如何促进动脉粥样硬化。
Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×105 DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE−/− mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis.