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

Official URL:https://doi.org/10.1038/ni.1789
PubMed:View item in PubMed
Creators Name:van de Pavert, S.A. and Olivier, B.J. and Goverse, G. and Vondenhoff, M.F. and Greuter, M. and Beke, P. and Kusser, K. and Hoepken, U.E. and Lipp, M. and Niederreither, K. and Blomhoff, R. and Sitnik, K. and Agace, W.W. and Randall, T.D. and de Jonge, W.J. and Mebius, R.E.
Journal Title:Nature Immunology
Journal Abbreviation:Nat Immunol
Page Range:1193-1199
Date:November 2009
Keywords:Aldehyde Dehydrogenase, Cell Differentiation, Cell Movement, Cultured Cells, Chemokine CCL21, Chemokine CXCL13, Mammalian Embryo, Isoenzymes, Lymph Nodes, Lymphoid Tissue, Neurons, Stromal Cells, Tretinoin, Vagus Nerve Stimulation, Animals, Mice
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.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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