Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis.
Fiche publication
Date publication
juillet 2017
Journal
Immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MUELLER Christopher
Tous les auteurs :
Onder L, Mörbe U, Pikor N, Novkovic M, Cheng HW, Hehlgans T, Pfeffer K, Becher B, Waisman A, Rülicke T, Gommerman J, Mueller CG, Sawa S, Scandella E, Ludewig B
Lien Pubmed
Résumé
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.
Mots clés
fibroblastic reticular cells, lymph node organogenesis, lymphatic and blood endothelial cells, lymphoid stromal cells, lymphoid tissue organizer cells, mesenchymal stromal cells
Référence
Immunity. 2017 07 18;47(1):80-92.e4