Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes.,PLOS Biology

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Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes.
PLOS Biology ( IF 7.8 ) Pub Date : 2020-04-06 , DOI: 10.1371/journal.pbio.3000704
Noriki Fujimoto _{1,

2} , Yuliang He ₁ , Marco D'Addio ₁ , Carlotta Tacconi ₁ , Michael Detmar ₁ , Lothar C Dieterich ₁

Affiliation

Lymph nodes (LNs) are highly organized secondary lymphoid organs that mediate adaptive immune responses to antigens delivered via afferent lymphatic vessels. Lymphatic endothelial cells (LECs) line intranodal lymphatic sinuses and organize lymph and antigen distribution. LECs also directly regulate T cells, mediating peripheral tolerance to self-antigens, and play a major role in many diseases, including cancer metastasis. However, little is known about the phenotypic and functional heterogeneity of LN LECs. Using single-cell RNA sequencing, we comprehensively defined the transcriptome of LECs in murine skin-draining LNs and identified new markers and functions of distinct LEC subpopulations. We found that LECs residing in the subcapsular sinus (SCS) have an unanticipated function in scavenging of modified low-density lipoprotein (LDL) and also identified a specific cortical LEC subtype implicated in rapid lymphocyte egress from LNs. Our data provide new, to our knowledge, insights into the diversity of LECs in murine LNs and a rich resource for future studies into the regulation of immune responses by LN LECs.

中文翻译：

单细胞作图揭示了淋巴结中淋巴管内皮细胞的新标志物和功能。

淋巴结（LNs）是高度组织化的次要淋巴器官，介导对通过传入淋巴管递送的抗原的适应性免疫反应。淋巴管内皮细胞（LECs）结节内淋巴窦并组织淋巴液和抗原分布。LEC还直接调节T细胞，介导外周对自身抗原的耐受，并在包括癌症转移在内的许多疾病中起主要作用。但是，关于LN LEC的表型和功能异质性知之甚少。使用单细胞RNA测序，我们全面定义了小鼠皮肤引流性LN中LEC的转录组，并鉴定了不同LEC亚群的新标记和功能。我们发现，位于囊下窦（SCS）中的LEC在清除修饰的低密度脂蛋白（LDL）方面具有意想不到的功能，并且还鉴定了涉及从LNs快速淋巴细胞排出的特定皮质LEC亚型。就我们所知，我们的数据提供了关于小鼠LN中LEC多样性的新见解，并为将来研究LN LEC调节免疫应答提供了丰富的资源。

更新日期：2020-04-06

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