van de Pavert Serge A, Olivier Brenda J, Goverse Gera, Vondenhoff Mark F, Greuter Mascha, Beke Patrick, Kusser Kim, Höpken Uta E, Lipp Martin, Niederreither Karen, Blomhoff Rune, Sitnik Kasia, Agace William W, Randall Troy D, de Jonge Wouter J, Mebius Reina E
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Nat Immunol. 2009 Nov;10(11):1193-9. doi: 10.1038/ni.1789. Epub 2009 Sep 27.
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.
胚胎淋巴结发育的位置由淋巴组织诱导细胞（LTi）的初始聚集所决定。在此我们证明，趋化因子CXCL13和趋化因子CCL21在胚胎发育第12.5至14.5天吸引LTi细胞，且初始聚集完全依赖于CXCL13。视黄酸（RA）在不依赖淋巴毒素信号传导的情况下，诱导基质组织细胞早期表达CXCL13。值得注意的是，与淋巴结原基相邻的神经元表达RA合成所必需的酶。此外，对成年动物副交感神经输出的刺激导致肠道中CXCL13的RA受体（RAR）依赖性诱导。因此，我们的数据表明，淋巴结发育的起始受RA介导的CXCL13表达控制，并提示RA可能由相邻神经元提供。
