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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)80-92.e4
JournalImmunity
Volume47
Issue number1
DOIs
Publication statusPublished - Jul 18 2017

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Organogenesis
Lymphoid Tissue
Endothelial Cells
Lymph Nodes
Helper-Inducer T-Lymphocytes
Lysosphingolipid Receptors
Lymphatic System
Histocompatibility Antigens Class II
Mesenchymal Stromal Cells
Blood Vessels

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Onder, L., Mörbe, U., Pikor, N., Novkovic, M., Cheng, H. W., Hehlgans, T., ... Ludewig, B. (2017). Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis. Immunity, 47(1), 80-92.e4. https://doi.org/10.1016/j.immuni.2017.05.008

Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis. / Onder, Lucas; Mörbe, Urs; Pikor, Natalia; Novkovic, Mario; Cheng, Hung Wei; Hehlgans, Thomas; Pfeffer, Klaus; Becher, Burkhard; Waisman, Ari; Rülicke, Thomas; Gommerman, Jennifer; Mueller, Christopher G.; Sawa, Shinichiro; Scandella, Elke; Ludewig, Burkhard.

In: Immunity, Vol. 47, No. 1, 18.07.2017, p. 80-92.e4.

Research output: Contribution to journalArticle

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 2017, 'Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis', Immunity, vol. 47, no. 1, pp. 80-92.e4. https://doi.org/10.1016/j.immuni.2017.05.008
Onder L, Mörbe U, Pikor N, Novkovic M, Cheng HW, Hehlgans T et al. Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis. Immunity. 2017 Jul 18;47(1):80-92.e4. https://doi.org/10.1016/j.immuni.2017.05.008
Onder, Lucas ; Mörbe, Urs ; Pikor, Natalia ; Novkovic, Mario ; Cheng, Hung Wei ; Hehlgans, Thomas ; Pfeffer, Klaus ; Becher, Burkhard ; Waisman, Ari ; Rülicke, Thomas ; Gommerman, Jennifer ; Mueller, Christopher G. ; Sawa, Shinichiro ; Scandella, Elke ; Ludewig, Burkhard. / Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis. In: Immunity. 2017 ; Vol. 47, No. 1. pp. 80-92.e4.
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