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Cell Rep. 2019 Mar 12;26(11):3116-3131.e5. doi: 10.1016/j.celrep.2019.02.042.

Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes.

Author information

1
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
2
Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), UMR1048, INSERM, UPS, Toulouse, France; Plateforme Genome et Transcriptome (GeT), Genopole Toulouse, Toulouse, France.
3
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France. Electronic address: jean-philippe.girard@ipbs.fr.

Abstract

High-endothelial venules (HEVs) are specialized blood vessels allowing recirculation of naive lymphocytes through lymphoid organs. Here, using full-length, single-cell RNA sequencing, RNA fluorescence in situ hybridization (FISH), flow cytometry, and immunohistofluorescence, we reveal the heterogeneity of HEVs in adult mouse peripheral lymph nodes (PLNs) under conditions of homeostasis, antigenic stimulation, and after inhibition of lymphotoxin-β receptor (LTβR) signaling. We demonstrate that HEV endothelial cells are in an activated state during homeostasis, and we identify the genes characteristic of the differentiated HEV phenotype. We show that LTβR signaling regulates many HEV genes and pathways in resting PLNs and that immune stimulation induces a global and temporary inflammatory phenotype in HEVs without compromising their ability to recruit naive lymphocytes. Most importantly, we uncover differences in the regulation of genes controlling lymphocyte trafficking, Glycam1, Fut7, Gcnt1, Chst4, B3gnt3, and Ccl21a, that have implications for HEV function and regulation in health and disease.

KEYWORDS:

endothelial cell; high-endothelial venule; homeostasis; inflammation; lymphocyte homing; lymphocyte trafficking; lymphotoxin-beta receptor; peripheral lymph node; scRNA-seq; single-cell RNA sequencing

PMID:
30865898
DOI:
10.1016/j.celrep.2019.02.042
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