Foxp3-positive macrophages display immunosuppressive properties and promote tumor growth.
Foxp3-positive macrophages display immunosuppressive properties and promote tumor growth.
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DOI：
10.1084/jem.20100730
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发表时间：
2011-07-04
期刊：
影响因子：
--
通讯作者：
Lustgarten J
中科院分区：
文献类型：
--
作者：
Manrique SZ;Correa MA;Hoelzinger DB;Dominguez AL;Mirza N;Lin HH;Stein-Streilein J;Gordon S;Lustgarten J
foxp3表达抑制巨噬细胞群体的鉴定。调节性T细胞（Regulatory T cells, T reg cells）以表达叉头谱系特异性转录因子Foxp3为特征，其主要功能是抑制T细胞。在评估T regg细胞时，我们发现foxp3阳性细胞群为CD11b+F4/80+CD68+，表明巨噬细胞起源。在幼年动物的脾脏、淋巴结、骨髓、胸腺、肝脏等组织中均可见到这些细胞。为了表征这一巨噬细胞亚群，我们设计了一种利用Foxp3- gfp小鼠纯化CD11b+F4/80+Foxp3+巨噬细胞的策略。CD11b+F4/80+Foxp3+巨噬细胞功能分析表明，这些细胞抑制T细胞的增殖，而Foxp3−巨噬细胞则没有。T细胞增殖抑制是通过可溶性因子介导的。Foxp3−巨噬细胞在激活后获得Foxp3表达，这赋予了与天然Foxp3+巨噬细胞难以区分的抑制特性。Foxp3+巨噬细胞的细胞因子和转录谱与Foxp3−巨噬细胞不同，表明这些细胞具有不同的生物学功能。体内功能分析表明CD11b+F4/80+Foxp3+巨噬细胞在促进肿瘤和诱导T细胞转化中起重要作用。这些研究首次证明了天然巨噬细胞调节细胞中存在一个独特的亚群，其中Foxp3的表达与抑制功能相关。
Identification of a population of Foxp3-expressing suppressive macrophages. Regulatory T cells (T reg cells) are characterized by the expression of the forkhead lineage-specific transcription factor Foxp3, and their main function is to suppress T cells. While evaluating T reg cells, we identified a population of Foxp3-positive cells that were CD11b+F4/80+CD68+, indicating macrophage origin. These cells were observed in spleen, lymph nodes, bone marrow, thymus, liver, and other tissues of naive animals. To characterize this subpopulation of macrophages, we devised a strategy to purify CD11b+F4/80+Foxp3+ macrophages using Foxp3-GFP mice. Analysis of CD11b+F4/80+Foxp3+ macrophage function indicated that these cells inhibited the proliferation of T cells, whereas Foxp3− macrophages did not. Suppression of T cell proliferation was mediated through soluble factors. Foxp3− macrophages acquired Foxp3 expression after activation, which conferred inhibitory properties that were indistinguishable from natural Foxp3+ macrophages. The cytokine and transcriptional profiles of Foxp3+ macrophages were distinct from those of Foxp3− macrophages, indicating that these cells have different biological functions. Functional in vivo analyses indicated that CD11b+F4/80+Foxp3+ macrophages are important in tumor promotion and the induction of T reg cell conversion. For the first time, these studies demonstrate the existence of a distinct subpopulation of naturally occurring macrophage regulatory cells in which expression of Foxp3 correlates with suppressive function.
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影响因子：
32.4
作者：
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