MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland.
Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
Immunity. 2019 Sep 17;51(3):561-572.e5. doi: 10.1016/j.immuni.2019.06.027. Epub 2019 Aug 8.
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.
淋巴管是调节人体健康和疾病的关键组成部分。尽管它们的功能意义越来越受到重视，但淋巴管的全面异质性仍未得到描述。在这里，我们通过单细胞 RNA 测序对人类淋巴结（LN）中的 33,000 个淋巴管内皮细胞（LEC）进行了分析。无偏聚类揭示了六种主要类型的人 LEC。LN 被膜下窦（SCS）内皮细胞丰富表达中性粒细胞趋化因子，而 LN 髓窦（MS）内皮细胞表达 C 型凝集素 CD209。碳水化合物路易斯 X（CD15）与 CD209 的结合介导中性粒细胞与 MS 的结合。MS LEC 对中性粒细胞的选择性归巢可能使中性粒细胞保留在 LN 髓质中，并允许淋巴携带的病原体清除，防止其在人类 LN 中传播。我们的研究提供了 LEC 异质性的全面特征，并揭示了髓质 LEC 在人类免疫中的以前未定义的作用。
