Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation.
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.
Serge A
SA
van de Pavert
Brenda J
BJ
Olivier
Gera
G
Goverse
Mark F
MF
Vondenhoff
Mascha
M
Greuter
Patrick
P
Beke
Kim
K
Kusser
Uta E
UE
Höpken
Martin
M
Lipp
Karen
K
Niederreither
Rune
R
Blomhoff
Kasia
K
Sitnik
William W
WW
Agace
Troy D
TD
Randall
Wouter J
WJ
de Jonge
Reina E
RE
Mebius
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008198:Lymph Nodes / Q000196:embryology*; D008221:Lymphoid Tissue / Q000196:embryology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D050697:Retinal Dehydrogenase; D017154:Stromal Cells / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D055536:Vagus Nerve Stimulation
D054421:Chemokine CCL21; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D007527:Isoenzymes; D014212:Tretinoin; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase