Inflammatory Chemokine Receptors Support Inflammatory Macrophage and Dendritic Cell Maturation.
Inflammatory Chemokine Receptors Support Inflammatory Macrophage and Dendritic Cell Maturation.
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DOI：
10.4049/immunohorizons.2200069
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发表时间：
2022-11-01
期刊：
影响因子：
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通讯作者：
Graham, Gerard J
中科院分区：
文献类型：
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作者：
Bartolini, Robin;Medina-Ruiz, Laura;Graham, Gerard J
树突状细胞在体内形成簇，但其背后的机制尚未确定。在这篇文章中，我们证明了单核细胞缺乏趋化因子受体CCR 1，CCR 2，CCR 3，和CCR 5显示在体外，这是与受损的树突状细胞和巨噬细胞分化减少群集。我们进一步表明，分化细胞本身产生的这些受体的功能，在一个冗余的方式，以调节细胞群集的配体。需要缺失或药理学阻断这些受体中的一种以上以损害群集和分化。我们的数据表明，趋化因子及其受体通过增加细胞表面整合素的表达和激活来支持聚类，细胞表面整合素与细胞-细胞相互作用相关，并且在单核细胞分化的背景下，与Foxp 1的表达减少相关，Foxp 1是一种已知的单核细胞分化的转录抑制因子。因此，我们的数据提供了一种机制，即通常在炎症环境中发现的趋化因子及其受体可以相互作用，以促进小鼠单核细胞分化为巨噬细胞和树突状细胞。
Dendritic cells form clusters in vivo, but the mechanism behind this has not been determined. In this article, we demonstrate that monocytes from mice deficient in the chemokine receptors CCR1, CCR2, CCR3, and CCR5 display reduced clustering in vitro, which is associated with impaired dendritic cell and macrophage differentiation. We further show that the differentiating cells themselves produce ligands for these receptors that function, in a redundant manner, to regulate cell clustering. Deletion of, or pharmacological blockade of, more than one of these receptors is required to impair clustering and differentiation. Our data show that chemokines and their receptors support clustering by increasing expression of, and activating, cell-surface integrins, which are associated with cell-cell interactions and, in the context of monocyte differentiation, with reduced expression of Foxp1, a known transcriptional suppressor of monocyte differentiation. Our data therefore provide a mechanism whereby chemokines and their receptors typically found in inflammatory environments can interact to promote murine monocyte differentiation to macrophages and dendritic cells.