Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils

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.

Keywords: cell adhesion; heterogeneity; human immunity; leukocyte trafficking; lymph nodes; lymphatic endothelial cells; lymphatic vessels; lymphatics; neutrophils; single-cell RNA-seq.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion Molecules / immunology
  • Cells, Cultured
  • Endothelial Cells / immunology*
  • Humans
  • Lectins, C-Type / immunology
  • Lewis X Antigen / immunology
  • Lymph Nodes / immunology
  • Lymphatic Vessels / immunology
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Receptors, Cell Surface / immunology
  • Surveys and Questionnaires


  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Lewis X Antigen
  • Receptors, Cell Surface