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Nature Research, Nature Immunology, 11(10), p. 1193-1199, 2009

DOI: 10.1038/ni.1789

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Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation

Journal article published in 2009 by Serge A. van de Pavert ORCID, Brenda J. Olivier, Gera Goverse, Mark F. Vondenhoff, Mascha Greuter, Patrick Beke, Kim Kusser, Uta E. Hoepken, Uta E. Höpken, Martin Lipp, Karen Niederreither, Rune Blomhoff, Kasia Sitnik ORCID, William W. Agace, Troy D. Randall and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.