CD4+CD25+ 调节性 T 细胞在巨噬细胞源性泡沫细胞形成中的作用。
The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation.
机构信息
Department of Cardiology, Institute of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of ScienceTechnology, Wuhan, China.
出版信息
J Lipid Res. 2010 May;51(5):1208-17. doi: 10.1194/jlr.D000497. Epub 2009 Dec 10.
Abstract
Cluster of differentiation (CD)4+CD25+ regulatory T cells (Tregs) exert a suppressive activity on atherosclerosis, but the underlying mechanism remains unclear. Here, we investigated whether and how Tregs affect macrophages foam-cell formation. Tregs were isolated by magnetic cell sorting-column and analyzed by flow cytometry. Macrophages were cultured with or without Tregs in the presence of oxidized LDL (oxLDL) for 48 h to transform foam cells. After co-culture with Tregs, macrophages showed a decrease in lipid accumulation, which was accompanied by a significantly downregulated expression of CD36 and SRA but no obvious difference in ABCA1 expression. Tregs can inhibit the proinflammatory properties of macrophages and steer macrophage differentiation toward an anti-inflammatory cytokine producing phenotype. Mechanistic studies reveal that both cell-to-cell contact and soluble factors are required for Treg-mediated suppression on macrophage foam-cell formation. Cytokines, interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta) are the key factors for these suppressive functions.
摘要
CD4+CD25+调节性 T 细胞（Tregs）在动脉粥样硬化中发挥抑制作用，但具体机制尚不清楚。本研究旨在探讨 Tregs 是否以及如何影响巨噬细胞泡沫细胞的形成。采用磁珠细胞分选柱分离 Tregs，流式细胞术进行分析。将巨噬细胞与 Tregs 共培养或不共培养，加入氧化型低密度脂蛋白（oxLDL）孵育 48 h 以诱导泡沫细胞形成。与 Tregs 共培养后，巨噬细胞脂质蓄积减少，CD36 和 SRA 表达明显下调，ABCA1 表达无明显差异。Tregs 可抑制巨噬细胞的促炎特性，并促使巨噬细胞向产生抗炎细胞因子的表型分化。机制研究表明，Treg 介导的对巨噬细胞泡沫细胞形成的抑制作用需要细胞间接触和可溶性因子。细胞因子白细胞介素 10（IL-10）和转化生长因子-β（TGF-β）是这些抑制功能的关键因素。
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