Hyaluronan and Its Receptors: Key Mediators of Immune Cell Entry and Trafficking in the Lymphatic System.
Hyaluronan and Its Receptors: Key Mediators of Immune Cell Entry and Trafficking in the Lymphatic System.
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透明质酸及其受体：淋巴系统中免疫细胞进入和运输的关键介质。
DOI：
10.3390/cells10082061
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发表时间：
2021-08-12
期刊：
影响因子：
6
通讯作者：
Jackson DG
中科院分区：
文献类型：
--
作者：
Johnson LA;Jackson DG
进入传入淋巴管标志着免疫细胞从组织迁移到引流淋巴结的第一步，既可以产生免疫反应，也可以及时解决组织炎症。这一关键过程主要发生在初始毛细淋巴管中专门的不连续连接处，由淋巴内皮释放的趋化因子引导，并由淋巴受体与其免疫细胞配体之间的粘附精心策划。后者中最突出的是大糖胺聚糖透明质酸 (HA)，它可以在某些组织迁移白细胞的表面形成庞大的糖萼，并且其与其关键淋巴受体 LYVE-1 的结合介导树突状细胞与传入淋巴管的对接和进入。在这里，我们概述了 HA 糖萼与 LYVE-1 和相关白细胞受体 CD44 在免疫细胞进入中合作的分子机制的最新见解，以及 LYVE-1 • HA 结合相互作用的不寻常特征如何促进该过程。此外，我们描述了 HA 的促炎分解产物如何通过 LYVE-1 转导信号促进淋巴管生成和增加连接通透性，从而促进淋巴进入。最后，我们概述了一些未来的前景，并强调 LYVE-1 • HA 轴作为免疫治疗的潜在靶点。
Entry to the afferent lymphatics marks the first committed step for immune cell migration from tissues to draining lymph nodes both for the generation of immune responses and for timely resolution of tissue inflammation. This critical process occurs primarily at specialised discontinuous junctions in initial lymphatic capillaries, directed by chemokines released from lymphatic endothelium and orchestrated by adhesion between lymphatic receptors and their immune cell ligands. Prominent amongst the latter is the large glycosaminoglycan hyaluronan (HA) that can form a bulky glycocalyx on the surface of certain tissue-migrating leucocytes and whose engagement with its key lymphatic receptor LYVE-1 mediates docking and entry of dendritic cells to afferent lymphatics. Here we outline the latest insights into the molecular mechanisms by which the HA glycocalyx together with LYVE-1 and the related leucocyte receptor CD44 co-operate in immune cell entry, and how the process is facilitated by the unusual character of LYVE-1 • HA-binding interactions. In addition, we describe how pro-inflammatory breakdown products of HA may also contribute to lymphatic entry by transducing signals through LYVE-1 for lymphangiogenesis and increased junctional permeability. Lastly, we outline some future perspectives and highlight the LYVE-1 • HA axis as a potential target for immunotherapy.
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