Centre d Immunologie de Marseille-Luminy, CIML, Aix Marseille Univ, CNRS, INSERM, Marseille, France.
Mucosal Immunol. 2017 Nov;10(6):1412-1430. doi: 10.1038/mi.2017.30. Epub 2017 Apr 5.
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 SIRPα 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 CD8α interfollicular cDC number, and (iii) activation of both CD11b and CD8α 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.
派尔集合淋巴结（PP）黏膜免疫应答的启动依赖于树突状细胞（DCs）对外源抗原的摄取、加工和有效呈递。在 PP DC 中，CD11b 传统型 DC（cDC）和表达溶酶体的 DC（LysoDC）具有不同的前体和功能，但具有许多细胞表面标记。这以前导致了这两个亚群之间的混淆。此外，另一个 PP DC 亚群，称为双阴性（DN），仍然特征不足。在这里，我们表明 DN 和 CD11b cDC 都属于独特的 SIRPα cDC 亚群。在稳态下，cDC 和 TIM-4 巨噬细胞主要位于 T 细胞区，即滤泡间区，而大多数黏膜下吞噬细胞是单核细胞衍生的细胞，即 LysoDC 和 TIM-4 巨噬细胞。最后，Toll 样受体 7 配体的口服给药至少诱导了三个 TNF 依赖性事件：（i）穹顶相关绒毛 cDC 向滤泡间区的迁移，（ii）滤泡间区 CD8α cDC 数量的增加，以及（iii）CD11b 和 CD8α 滤泡间 cDC 的激活。后者的特征是遗传重编程，导致 I 型干扰素刺激和免疫刺激和抑制基因表达的上调。
