Origins and Functional Specialization of Macrophages and of Conventional and Monocyte-Derived Dendritic Cells in Mouse Skin

Origins and Functional Specialization of Macrophages and of Conventional and Monocyte-Derived Dendritic Cells in Mouse Skin
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DOI:
10.1016/j.immuni.2013.10.004
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发表时间:
2013-11-14
期刊:
影响因子:
32.4
通讯作者:
Henri, Sandrine
Henri, Sandrine
中科院分区:
医学1区
文献类型:
--
作者:
Tamoutounour, Samira;Guilliams, Martin;Henri, Sandrine

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在皮肤中,缺乏能够明确识别巨噬细胞和常规和单核细胞来源的树突状细胞(DC)的标志物,使得对它们对皮肤完整性和免疫反应的贡献的理解变得复杂。通过结合CD64和CCR2染色,我们成功地鉴定了这些细胞类型,并研究了它们的来源、转录特征以及迁移和T细胞刺激特性。我们还分析了微生物区系对其发育的影响,以及它们在接触性超敏反应中对皮肤炎症的贡献。真皮巨噬细胞具有独特的清除作用,不能迁移和激活T细胞。传统的真皮树突状细胞在迁移和激活T细胞方面表现出色。在稳定状态的真皮中,渗出的Ly-6C(Hi)单核细胞持续产生单核细胞来源的DC。它们的T细胞刺激能力与其较差的迁移能力相结合,使它们特别适合于激活亲皮肤的T细胞。因此,皮肤的单核吞噬细胞之间发生了高度的功能特化。
In the skin, the lack of markers permitting the unambiguous identification of macrophages and of conventional and monocyte-derived dendritic cells (DCs) complicates understanding of their contribution to skin integrity and to immune responses. By combining CD64 and CCR2 staining, we successfully identified each of these cell types and studied their origin, transcriptomic signatures, and migratory and T cell stimulatory properties. We also analyzed the impact of microbiota on their development and their contribution to skin inflammation during contact hypersensitivity. Dermal macrophages had a unique scavenging role and were unable to migrate and activate T cells. Conventional dermal DCs excelled both at migrating and activating T cells. In the steady-state dermis, monocyte-derived DCs are continuously generated by extravasated Ly-6C(hi) monocytes. Their T cell stimulatory capacity combined with their poor migratory ability made them particularly suited to activate skin-tropic T cells. Therefore, a high degree of functional specialization occurs among the mononuclear phagocytes of the skin.