Gut-draining mesenteric lymph nodes (mLNs) are important for inducing peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for de novo generation of Foxp3⁺ regulatory T cells (Tregs). We previously identified microbiota-imprinted mLN stromal cells as a critical component in tolerance induction. Here we show that this imprinting process already takes place in the neonatal phase, and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. LN transplantation and single-cell RNA-seq uncover stably imprinted expression signatures in mLN fibroblastic stromal cells. Subsetting common stromal cells across gut-draining mLNs and skin-draining LNs further refine their location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Finally, we demonstrate that mLN stromal cells shape resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust regulatory mechanism for the maintenance of intestinal tolerance.

中文翻译：

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新生儿印记的基质细胞亚群在肠系膜淋巴结中诱导耐受性树突状细胞。

肠内引流肠系膜淋巴结（mLNs）通过提供从头产生Foxp3 ⁺的最佳微环境，对于诱导周围对食物和共生抗原的耐受性非常重要调节性T细胞（Tregs）。我们先前确定微生物印记的mLN基质细胞为耐受诱导中的关键组成部分。在这里，我们表明这种印迹过程已经发生在新生儿阶段，并且使mLN基质细胞区室在以后的生活中对炎症扰动具有抵抗力。LN移植和单细胞RNA-seq在mLN成纤维细胞基质细胞中发现稳定印记的表达特征。跨肠引流的mLN和引流皮肤的LN的常见基质细胞亚群进一步完善了它们的位置特异性免疫调节功能，例如Aldh1a2 / 3的子集特异性表达。最后，我们证明mLN基质细胞塑造常驻树突状细胞，以依赖Bmp2的方式获得高Treg诱导能力。因此，