Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization
Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization
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DOI：
10.1016/j.immuni.2004.09.003
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发表时间：
2004-10-01
期刊：
影响因子：
32.4
通讯作者：
Randolph, GJ
中科院分区：
文献类型：
--
作者：
Angeli, V;Llodrá, J;Randolph, GJ
高 LDL 和/或低 HDL 是动脉粥样硬化的危险因素，也是系统性红斑狼疮、类风湿性关节炎和牛皮癣的常见临床特征。在这里，我们发现反映动脉粥样硬化疾病的脂质谱的变化导致局部皮肤鼠树突状细胞（DC）的激活，促进皮肤炎症，并诱导淋巴结肥大。矛盾的是，DC 向淋巴结的迁移受到损害，从而抑制了免疫启动。迁移受损是由血小板激活因子 (PAF) 或充当 PAF 模拟物的氧化 LDL 产生的抑制信号造成的。 HDL 或 HDL 相关的 PAF 乙酰水解酶 (PAFAH) 可恢复正常的 DC 迁移和启动，从而介导 PAF 和氧化 LDL 的失活。因此，动脉粥样硬化的变化可以将活化的树突状细胞隔离在外周，在那里它们可能会加重局部炎症，即使它们不能很好地执行需要迁移到淋巴结的功能。在这种情况下，HDL 和 PAFAH 维持 DC 室的正常功能。
High LDL and/or low HDL are risk factors for atherosclerosis and are also a common clinical feature in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Here, we show that changes in lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells (DCs) locally, promoted dermal inflammation, and induced lymph node hypertrophy. Paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic priming. Impaired migration resulted from inhibitory signals generated by platelet-activating factor (PAF) or oxidized LDL that acts as a PAF mimetic. Normal DC migration and priming was restored by HDL or HDL associated PAF acetylhydrolase (PAFAH), which mediates inactivation of PAF and oxidized LDL. Thus, atherosclerotic changes can sequester activated DCs in the periphery where they may aggravate local inflammation even as they poorly carry out functions that require their migration to lymph nodes. In this context, HDL and PAFAH maintain a normally functional DC compartment.