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肾脏树突状细胞:基础生物学及在健康和疾病中的功能作用。

Kidney dendritic cells: fundamental biology and functional roles in health and disease.

机构信息

Institute of Experimental Immunology, Rheinische Friedrich-Wilhelms-Universität, Venusbergcampus, Bonn, Germany.

Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Singapore, Singapore.

出版信息

Nat Rev Nephrol. 2020 Jul;16(7):391-407. doi: 10.1038/s41581-020-0272-y. Epub 2020 May 5.

Abstract

Dendritic cells (DCs) are chief inducers of adaptive immunity and regulate local inflammatory responses across the body. Together with macrophages, the other main type of mononuclear phagocyte, DCs constitute the most abundant component of the intrarenal immune system. This network of functionally specialized immune cells constantly surveys its microenvironment for signs of injury or infection, which trigger the initiation of an immune response. In the healthy kidney, DCs coordinate effective immune responses, for example, by recruiting neutrophils for bacterial clearance in pyelonephritis. The pro-inflammatory actions of DCs can, however, also contribute to tissue damage in various types of acute kidney injury and chronic glomerulonephritis, as DCs recruit and activate effector T cells, which release toxic mediators and maintain tubulointerstitial immune infiltrates. These actions are counterbalanced by DC subsets that promote the activation and maintenance of regulatory T cells to support resolution of the immune response and allow kidney repair. Several studies have investigated the multiple roles for DCs in kidney homeostasis and disease, but it has become clear that current tools and subset markers are not sufficient to accurately distinguish DCs from macrophages. Multidimensional transcriptomic analysis studies promise to improve mononuclear phagocyte classification and provide a clearer view of DC ontogeny and subsets.

摘要

树突状细胞(DCs)是适应性免疫的主要诱导者,调节全身局部炎症反应。与巨噬细胞一起,作为另一种主要的单核吞噬细胞,DCs构成了肾脏内免疫系统中最丰富的成分。这个功能特化免疫细胞网络不断监测其微环境中是否存在损伤或感染的迹象,这些迹象会引发免疫反应的启动。在健康的肾脏中,DCs 协调有效的免疫反应,例如,在肾盂肾炎中招募中性粒细胞进行细菌清除。然而,DCs 的促炎作用也可能导致各种类型的急性肾损伤和慢性肾小球肾炎中的组织损伤,因为 DCs 招募和激活效应 T 细胞,这些细胞释放毒性介质并维持肾小管间质免疫浸润。这些作用被促进调节性 T 细胞激活和维持的 DC 亚群所抵消,以支持免疫反应的解决并允许肾脏修复。多项研究调查了 DCs 在肾脏稳态和疾病中的多种作用,但很明显,目前的工具和亚群标记物不足以准确区分 DCs 和巨噬细胞。多维转录组分析研究有望改善单核吞噬细胞分类,并更清楚地了解 DC 发生和亚群。

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