Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils
Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils
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DOI：
10.1016/j.immuni.2019.06.027
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发表时间：
2019-09-17
期刊：
影响因子：
32.4
通讯作者：
Jalkanen, Sirpa
中科院分区：
文献类型：
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作者：
Takeda, Akira;Hollmen, Maija;Jalkanen, Sirpa
淋巴管是调节人类健康和疾病的重要组成部分。虽然它们的功能意义越来越被认识到，但淋巴管的综合异质性仍未被表征。在这里，我们报告了通过单细胞RNA测序对人类淋巴结（LNs）中33,000淋巴内皮细胞（LECs）的分析。无偏聚类揭示了人类LECs的六种主要类型。囊下窦（SCS）内的上皮细胞大量表达中性粒细胞趋化剂，而髓质窦（MS）内的上皮细胞表达c型凝集素CD209。MS LECs的中性粒细胞选择性归巢可能保留LN髓质中的中性粒细胞，并允许淋巴传播的病原体清除，防止它们在人类LN中传播。我们的研究提供了LEC异质性的全面表征，并揭示了髓质LEC在人类免疫中的先前未定义的作用。
Lymphatic vessels form a critical component in the regulation of human health and disease. While their functional significance is increasingly being recognized, the comprehensive heterogeneity of lymphatics remains uncharacterized. Here, we report the profiling of 33,000 lymphatic endothelial cells (LECs) in human lymph nodes (LNs) by single-cell RNA sequencing. Unbiased clustering revealed six major types of human LECs. LECs lining the subcapsular sinus (SCS) of LNs abundantly expressed neutrophil chemoattractants, whereas LECs lining the medullary sinus (MS) expressed a C-type lectin CD209. Binding of a carbohydrate Lewis X (CD15) to CD209 mediated neutrophil binding to the MS. The neutrophil-selective homing by MS LECs may retain neutrophils in the LN medulla and allow lymph-borne pathogens to clear, preventing their spread through LNs in humans. Our study provides a comprehensive characterization of LEC heterogeneity and unveils a previously undefined role for medullary LECs in human immunity.