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健康和动脉粥样硬化小鼠主动脉中树突状细胞亚群分布

Dendritic cell subset distributions in the aorta in healthy and atherosclerotic mice.

作者信息

Busch Martin, Westhofen Thilo C, Koch Miriam, Lutz Manfred B, Zernecke Alma

机构信息

Rudolf Virchow-Center; University of Würzburg, Würzburg, Germany.

Rudolf Virchow-Center; University of Würzburg, Würzburg, Germany ; Institute of Clinical Biochemistry and Pathobiocchemistry, University Hospital Würzburg, Würzburg, Germany.

出版信息

PLoS One. 2014 Feb 14;9(2):e88452. doi: 10.1371/journal.pone.0088452. eCollection 2014.

Abstract

Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr (-/-)) mice, CD11c(+) MHCII(+) DCs could be discriminated into CD103(-) CD11b(+)F4/80(+), CD11b(+)F4/80(-) and CD11b(-)F4/80(-) DCs and CD103(+) CD11b(-)F4/80(-) DCs. Except for CD103(-) CD11b(-) F4/80(-) DCs, these subsets expanded in high fat diet-fed Ldlr (-/-) mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b(+) DCs, and partially on CD103(-) CD11b(-) F4/80(-) but not on CD103(+) DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l (-/-)) mice, a specific loss of CD103(+) DCs but also CD103(-) CD11b(+) F4/80(-) DCs was evidenced. Aortic CD103(+) and CD11b(+) F4/80(-) CD103(-) DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD103(-) CD11b(+) F4/80(-) and CD11b(+) F4/80(+) cells in atherosclerotic Ldlr (-/-) mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b(+) F4/80(-) DCs similar to CD11b(+) F4/80(+) DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation.

摘要

树突状细胞(DCs)可细分为多个亚群,它们在启动适应性免疫反应中发挥着特定作用。动脉粥样硬化被视为一种血管壁的慢性炎症性疾病,在未发炎和患病的动脉中均可发现DCs。我们在此对动脉粥样硬化形成过程中的DC亚群进行了系统分析。我们的数据表明,不同的DC亚群可定位于血管壁。在C57BL/6和低密度脂蛋白受体缺陷(Ldlr (-/-))小鼠中,CD11c(+) MHCII(+) DCs可分为CD103(-) CD11b(+)F4/80(+)、CD11b(+)F4/80(-)和CD11b(-)F4/80(-) DCs以及CD103(+) CD11b(-)F4/80(-) DCs。除了CD103(-) CD11b(-) F4/80(-) DCs外,这些亚群在高脂饮食喂养的Ldlr (-/-)小鼠中有所扩增。信号调节蛋白(Sirp)-α在主动脉巨噬细胞、CD11b(+) DCs上被检测到,在部分CD103(-) CD11b(-) F4/80(-) DCs上也有表达,但在CD103(+) DCs上未检测到。值得注意的是,在FMS样酪氨酸激酶3配体缺陷(Flt3l (-/-))小鼠中,证实了CD103(+) DCs以及CD103(-) CD11b(+) F4/80(-) DCs的特异性缺失。鉴于主动脉CD103(+)和CD11b(+) F4/80(-) CD103(-) DCs对Flt3L信号的依赖性,它们可能属于传统DCs而非单核细胞来源的DCs。假定用于区分巨噬细胞和DCs的CD64,在生理条件下的DC亚群中未被检测到,但在动脉粥样硬化的Ldlr (-/-)小鼠的一部分CD103(-) CD11b(+) F4/80(-)和CD11b(+) F4/80(+)细胞中出现。动脉粥样硬化中CD64表达的出现可能表明,类似于CD11b(+) F4/80(+) DCs的CD11b(+) F4/80(-) DCs至少部分源自动脉粥样硬化病变形成过程中迁移的单核细胞。我们的数据增进了我们对动脉粥样硬化中不同DC亚群的存在及其积累特征的了解,并可能有助于未来旨在基于特定DC的治疗策略治疗慢性血管炎症的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6095/3925240/0067cdfb88db/pone.0088452.g001.jpg

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