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

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...

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Bibliographic Details
Published in:PLoS biology Vol. 18; no. 4; p. e3000704
Main Authors: Fujimoto, Noriki, He, Yuliang, D’Addio, Marco, Tacconi, Carlotta, Detmar, Michael, Dieterich, Lothar C.
Format: Journal Article
Language:English
Published: United States Public Library of Science 06.04.2020
Public Library of Science (PLoS)
Subjects:
Adaptive immunity
Antigens
Autoantigens
Biology and Life Sciences
Cell adhesion & migration
Cell research
Cellular control mechanisms
Composition
Egress
Endothelial cells
Endothelium
Gene expression
Gene sequencing
Health aspects
Heterogeneity
Immune response
Immunological tolerance
Kinases
Low density lipoprotein
Lymph nodes
Lymphatic system
Lymphocytes
Lymphocytes T
Mapping
Markers
Medical examination
Medicine and Health Sciences
Metastases
Methods and Resources
Organs
Pharmaceutical sciences
Research and Analysis Methods
Ribonucleic acid
RNA
Scavenging
Sensory neurons
Sinuses
Subpopulations
United States
Switzerland
ISSN:1545-7885, 1544-9173, 1545-7885
Online Access:Get full text
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Description
Summary: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.
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The authors have declared that no competing interests exist.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3000704