Specialized stromal cells occupy and help define B- and T cell domains, which is crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF-receptors is crucial for development of different stromal subsets which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known. Here we show that in mice, retinoic acid mediated signaling is important for the differentiation of precursors towards the Cxcl13^pos follicular dendritic cell (FDC) lineage, while blocking lymphotoxin mediated Ccl19^pos fibroblastic reticular cell (FRC) lineage differentiation. Consequently, we see at day of birth Cxcl13^posCcl19^neg/low and Cxcl13^neg/lowCcl19^pos cells within neonatal lymph nodes. Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, while in addition, complete blockade of retinoic acid signaling prevents formation of FDC networks in lymph nodes.

中文翻译：

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淋巴结中滤泡性树突状细胞的发育取决于视黄酸介导的信号传导

专门的基质细胞占据并帮助定义B细胞和T细胞结构域，这对我们免疫系统的正常运转至关重要。通过淋巴毒素和TNF受体发出的信号对于不同基质亚群的发育至关重要，这些亚群被认为是由共同的前体产生的。但是，控制不同基质表型选择性生成的机制尚不清楚。在这里，我们显示在小鼠中，视黄酸介导的信号传导对于Cxcl13 ^pos滤泡树突状细胞（FDC）谱系前体的分化很重要，同时阻断淋巴毒素介导的Ccl19 ^pos纤维母细胞网状细胞（FRC）谱系分化。因此，我们在出生当天看到Cxcl13 ^pos Ccl19 ^{neg / low}和新生儿淋巴结内的Cxcl13 ^{neg / low} Ccl19 ^pos细胞。此外，出生后早期基质前体中的视黄酸受体信号传导消融可降低Cxcl13表达，此外，视黄酸信号传导的完全阻断可防止在淋巴结中形成FDC网络。