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Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis

Lucas Onder, Urs Mörbe, Natalia Pikor, Mario Novkovic, Hung-Wei Cheng, Thomas Hehlgans, Klaus Pfeffer, Burkhard Becher, Ari Waisman, Thomas Rülicke, Jennifer Gommerman, Christopher G Mueller, Shinichiro Sawa, Elke Scandella & Burkhard Ludewig

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.
   
citation Onder L, Mörbe U, Pikor N, Novkovic M, Cheng H W, Hehlgans T, Pfeffer K, Becher B, Waisman A, Rülicke T, Gommerman J, Mueller C G, Sawa S, Scandella E, Ludewig B. Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis. Immunity 2017; 47:80-92.e4.
   
type journal paper/review (English)
date of publishing 11-07-2017
journal title Immunity (47/1)
ISSN electronic 1097-4180
pages 80-92.e4
PubMed 28709801
DOI 10.1016/j.immuni.2017.05.008