Header

UZH-Logo

Maintenance Infos

Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis


Abstract

Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event. LEC activation was mediated mainly by signaling through receptor activator of NF-κB (RANK) and the non-canonical NF-κB pathway and was steered by sphingosine-1-phosphate-receptor-dependent retention of LTi cells in the LN anlage. Finally, the finding that pharmacologically enforced interaction between LTi cells and LECs promotes ectopic LN formation underscores the central LTo function of LECs.

Abstract

Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event. LEC activation was mediated mainly by signaling through receptor activator of NF-κB (RANK) and the non-canonical NF-κB pathway and was steered by sphingosine-1-phosphate-receptor-dependent retention of LTi cells in the LN anlage. Finally, the finding that pharmacologically enforced interaction between LTi cells and LECs promotes ectopic LN formation underscores the central LTo function of LECs.

Statistics

Citations

Dimensions.ai Metrics
17 citations in Web of Science®
7 citations in Scopus®
10 citations in Microsoft Academic
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Immunology, Immunology and Allergy, Infectious Diseases
Language:English
Date:18 July 2017
Deposited On:05 Oct 2017 13:28
Last Modified:19 Aug 2018 10:29
Publisher:Cell Press (Elsevier)
ISSN:1074-7613
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.immuni.2017.05.008
PubMed ID:28709801
Project Information:
  • : FunderSNSF
  • : Grant ID310030_146133
  • : Project TitleSelection and education of heart-specific Th cells by thymic and lymph node stromal cells
  • : FunderSNSF
  • : Grant IDCRSII3_141918
  • : Project TitleImaging-based Systems Biology Analysis of Lymph Node Structure and Function in Viral Infection

Download

Full text not available from this repository.
View at publisher

Get full-text in a library