Article abstract
Nature Immunology 10, 1193 - 1199 (2009)
Published online: 27 September 2009 | doi:10.1038/ni.1789
Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation
Serge A van de Pavert1, Brenda J Olivier1,8, Gera Goverse1,8, Mark F Vondenhoff1,8, Mascha Greuter1, Patrick Beke1, Kim Kusser2, Uta E Höpken3, Martin Lipp3, Karen Niederreither4, Rune Blomhoff5, Kasia Sitnik6, William W Agace6, Troy D Randall2, Wouter J de Jonge7 & Reina E Mebius1
Abstract
The location of embryonic lymph node development is determined by the initial clustering of lymphoid tissue–inducer (LTi) cells. Here we demonstrate that both the chemokine CXCL13 and the chemokine CCL21 attracted LTi cells at embryonic days 12.5–14.5 and that initial clustering depended exclusively on CXCL13. Retinoic acid (RA) induced early CXCL13 expression in stromal organizer cells independently of lymphotoxin signaling. Notably, neurons adjacent to the lymph node anlagen expressed enzymes essential for RA synthesis. Furthermore, stimulation of parasymphathetic neural output in adults led to RA receptor (RAR)-dependent induction of CXCL13 in the gut. Therefore, our data show that the initiation of lymph node development is controlled by RA-mediated expression of CXCL13 and suggest that RA may be provided by adjacent neurons.
- Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
- Department of Medicine, Division of Allergy, Immunology and Rheumatology, University of Rochester, Rochester, New York, USA.
- Max Delbrück Center for Molecular Medicine, Berlin, Germany.
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
- Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
- Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden.
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
- These authors contributed equally to this work.
Correspondence to: Reina E Mebius1 e-mail: r.mebius@vumc.nl
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