Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation
Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation
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DOI：
10.1038/mi.2017.30
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发表时间：
2017-11-01
影响因子：
8
通讯作者：
Lelouard, H.
中科院分区：
文献类型：
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作者：
Bonnardel, J.;Da Silva, C.;Lelouard, H.
派尔氏集结 (PP) 中粘膜免疫反应的启动依赖于树突状细胞 (DC) 的外源抗原的采样、处理和有效呈递。在 PP DC 中，CD11b(+) 常规 DC (cDC) 和表达溶菌酶的 DC (LysoDC) 具有不同的祖细胞和功能，但共享许多细胞表面标记。这之前导致了这两个子集之间的混淆。此外，另一个 PP DC 子集，称为双阴性 (DN)，仍然缺乏表征。在这里，我们表明 DN 和 CD11b(+) cDC 都属于独特的 SIRP alpha(+) cDC 子集。在稳定状态下，cDC和TIM-4(+)巨噬细胞主要位于T细胞区，即滤泡间区域，而大多数上皮下吞噬细胞是单核细胞来源的细胞，即LysoDC和TIM-4(+)巨噬细胞。最后，口服Toll样受体7配体诱导至少三种TNF依赖性事件：（i）圆顶相关绒毛cDC在滤泡间区域的迁移，（ii）CD8α（+）滤泡间cDC数量的增加，以及（iii）CD11α（+）和CD8α（+）滤泡间cDC的激活。后者的特点是基因重编程，导致 I 型干扰素刺激以及免疫刺激和抑制基因表达上调。
The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b(+) conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b(+) cDCs belong to a unique SIRP alpha(+) cDC subset. At steady state, cDCs and TIM-4(+) macrophages are mainly located in T-cell zones, i.e., interfollicular regions, whereas a majority of subepithelial phagocytes are monocyte-derived cells, namely, LysoDCs and TIM-4(+) macrophages. Finally, oral administration of a Toll-like receptor 7 ligand induces at least three TNF-dependent events: (i) migration of dome-associated villus cDCs in interfollicular regions, (ii) increase of CD8 alpha(+) interfollicular cDC number, and (iii) activation of both CD11 alpha(+) and CD8 alpha(+) interfollicular cDCs. The latter is marked by a genetic reprograming leading to the upregulation of type I interferon-stimulated and of both immuno-stimulatory and -inhibitory gene expression.