Publication
Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis
Journal Paper/Review - Jul 11, 2017
Onder Lucas, Scandella Elke, Sawa Shinichiro, Mueller Christopher G, Gommerman Jennifer, Rülicke Thomas, Waisman Ari, Becher Burkhard, Pfeffer Klaus, Hehlgans Thomas, Cheng Hung-Wei, Novkovic Mario, Pikor Natalia, Mörbe Urs, Ludewig Burkhard
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
Brief description/objective
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.