Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Infection and Immunity Institute, 1081HZ Amsterdam, the Netherlands.
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Development. 2021 Oct 15;148(20). doi: 10.1242/dev.199713. Epub 2021 Oct 26.
Specialized stromal cells occupy and help define B- and T-cell domains, which are crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF receptors is crucial for the 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. Using in vitro cultures of embryonic mouse stromal cells, we show that retinoic acid-mediated signaling is important for the differentiation of precursors towards the Cxcl13pos follicular dendritic cell (FDC) lineage, and also blocks lymphotoxin-mediated Ccl19pos fibroblastic reticular cell lineage differentiation. Accordingly, at the day of birth we observe the presence of Cxcl13posCcl19neg/low and Cxcl13neg/lowCcl19pos cells within neonatal lymph nodes. Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, and complete blockade of retinoic acid signaling prevents the formation of FDC networks in lymph nodes.
特异性基质细胞占据并有助于定义 B 细胞和 T 细胞区域，这对于我们的免疫系统的正常功能至关重要。通过淋巴毒素和 TNF 受体的信号传导对于不同基质细胞亚群的发育至关重要，这些亚群被认为来自共同的前体。然而，控制不同基质表型选择性产生的机制尚不清楚。我们使用胚胎鼠基质细胞的体外培养，表明视黄酸介导的信号对于前体细胞向 Cxcl13pos 滤泡树突状细胞（FDC）谱系的分化很重要，并且还阻止了淋巴毒素介导的 Ccl19pos 纤维母细胞网状细胞谱系分化。因此，在出生当天，我们观察到新生淋巴结内存在 Cxcl13posCcl19neg/low 和 Cxcl13neg/lowCcl19pos 细胞。此外，出生后早期基质前体细胞中视黄酸受体信号的缺失会降低 Cxcl13 的表达，而完全阻断视黄酸信号会阻止淋巴结中 FDC 网络的形成。
