Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland.
Department of Dermatology, Shiga University of Medical Sciences, Japan.
PLoS Biol. 2020 Apr 6;18(4):e3000704. doi: 10.1371/journal.pbio.3000704. eCollection 2020 Apr.
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.
淋巴结 (LNs) 是高度组织化的次级淋巴器官,可通过输入淋巴管传递的抗原介导适应性免疫反应。淋巴内皮细胞 (LECs) 排列在淋巴结内的淋巴窦中,并组织淋巴和抗原分布。LECs 还直接调节 T 细胞,介导对自身抗原的外周耐受,并在许多疾病中发挥主要作用,包括癌症转移。然而,人们对 LN LEC 的表型和功能异质性知之甚少。我们使用单细胞 RNA 测序全面定义了鼠皮肤引流淋巴结中 LEC 的转录组,并鉴定了不同 LEC 亚群的新标记物和功能。我们发现,位于被膜下窦 (SCS) 中的 LEC 具有清除修饰的低密度脂蛋白 (LDL) 的意外功能,并且还鉴定出一种特定的皮质 LEC 亚型,该亚型与淋巴细胞从淋巴结快速流出有关。我们的数据为 LN LECs 中 LEC 的多样性提供了新的、据我们所知的见解,并为未来研究 LN LECs 对免疫反应的调节提供了丰富的资源。
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