Onder, Lucas; Danuser, Renzo; Scandella, Elke; Firner, Sonja; Chai, Qian; Hehlgans, Thomas; Stein, Jens Volker; Ludewig, Burkhard (2013). Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation. The Journal of experimental medicine, 210(3), pp. 465-473. Rockefeller Univ. Press 10.1084/jem.20121462
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The development of lymph nodes (LNs) and formation of LN stromal cell microenvironments is dependent on lymphotoxin-β receptor (LTβR) signaling. In particular, the LTβR-dependent crosstalk between mesenchymal lymphoid tissue organizer and hematopoietic lymphoid tissue inducer cells has been regarded as critical for these processes. Here, we assessed whether endothelial cell (EC)-restricted LTβR signaling impacts on LN development and the vascular LN microenvironment. Using EC-specific ablation of LTβR in mice, we found that conditionally LTβR-deficient animals failed to develop a significant proportion of their peripheral LNs. However, remnant LNs showed impaired formation of high endothelial venules (HEVs). Venules had lost their cuboidal shape, showed reduced segment length and branching points, and reduced adhesion molecule and constitutive chemokine expression. Due to the altered EC-lymphocyte interaction, homing of lymphocytes to peripheral LNs was significantly impaired. Thus, this study identifies ECs as an important LTβR-dependent lymphoid tissue organizer cell population and indicates that continuous triggering of the LTβR on LN ECs is critical for lymphocyte homeostasis.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Danuser, Renzo, Stein, Jens Volker |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1540-9538 |
Publisher: |
Rockefeller Univ. Press |
Language: |
English |
Submitter: |
Ursula Zingg-Zünd |
Date Deposited: |
13 Jun 2014 16:20 |
Last Modified: |
05 Dec 2022 14:32 |
Publisher DOI: |
10.1084/jem.20121462 |
PubMed ID: |
23420877 |
BORIS DOI: |
10.7892/boris.48606 |
URI: |
https://boris.unibe.ch/id/eprint/48606 |