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

PLoS Biol. 2020 Apr 6;18(4):e3000704. doi: 10.1371/journal.pbio.3000704. eCollection 2020 Apr.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Endothelial Cells / cytology
  • Endothelium, Lymphatic / cytology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Integrin alpha2 / genetics
  • Lymph Nodes / cytology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Receptors, CCR / genetics
  • Receptors, CCR / metabolism
  • Sequence Analysis, RNA
  • Single-Cell Analysis / methods*
  • Vesicular Transport Proteins / genetics

Substances

  • Ackr4 protein, mouse
  • Biomarkers
  • Integrin alpha2
  • LYVE1 protein, mouse
  • Receptors, CCR
  • Vesicular Transport Proteins

Grants and funding

1. Krebsliga Zurich, no grant number, https://krebs-kommission.ch/ (to LCD). 2. Vontobel Foundation, no grant number, https://www.vontobel-stiftung.ch/DE/Home (to LCD). 3. Swiss National Science Foundation grants 310030_166490 and 310030B_185392, http://www.snf.ch (to MD). 4. European Research Council grant LYVICAM, https://erc.europa.eu (to MD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.