Chemokine CXCL13 is Essential for Lymph Node Initiation and is Induced by Retinoic Acid and Neuronal Stimulation

Overview

Journal Nat Immunol

Date 2009 Sep 29

PMID 19783990

Citations 146

Authors

Serge A van de Pavert

Brenda J Olivier

Gera Goverse

Mark F Vondenhoff

Mascha Greuter

Patrick Beke

Kim Kusser

Uta E Hopken

Martin Lipp

Karen Niederreither

Rune Blomhoff

Kasia Sitnik

William W Agace

Troy D Randall

Wouter J de Jonge

Reina E Mebius

Affiliations

Soon will be listed here.

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.

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