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M 细胞成熟和 cDC 活化决定新生儿派尔集合淋巴结适应性免疫启动的时机。

M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer's patch.

机构信息

Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen 52074, Germany.

Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen 52074, Germany.

出版信息

Immunity. 2023 Jun 13;56(6):1220-1238.e7. doi: 10.1016/j.immuni.2023.04.002. Epub 2023 May 1.

DOI:10.1016/j.immuni.2023.04.002
PMID:
37130522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10262694/
Abstract

Early-life immune development is critical to long-term host health. However, the mechanisms that determine the pace of postnatal immune maturation are not fully resolved. Here, we analyzed mononuclear phagocytes (MNPs) in small intestinal Peyer's patches (PPs), the primary inductive site of intestinal immunity. Conventional type 1 and 2 dendritic cells (cDC1 and cDC2) and RORgt+ antigen-presenting cells (RORgt+ APC) exhibited significant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, subsequently resulting in a lack in CD4+ T cell priming during the postnatal period. Microbial cues contributed but could not fully explain the discrepancies in MNP maturation. Type I interferon (IFN) accelerated MNP maturation but IFN signaling did not represent the physiological stimulus. Instead, follicle-associated epithelium (FAE) M cell differentiation was required and sufficient to drive postweaning PP MNP maturation. Together, our results highlight the role of FAE M cell differentiation and MNP maturation in postnatal immune development.

摘要

早期免疫发育对宿主的长期健康至关重要。然而，决定出生后免疫成熟速度的机制尚未完全解决。在这里，我们分析了小肠派尔集合淋巴结（PP）中的单核吞噬细胞（MNPs），这是肠道免疫的主要诱导部位。传统的 1 型和 2 型树突状细胞（cDC1 和 cDC2）和 RORγt+抗原呈递细胞（RORγt+APC）在亚群组成、组织分布和细胞成熟减少方面表现出显著的年龄依赖性变化，随后导致在出生后期间缺乏 CD4+T细胞的启动。微生物线索有贡献，但不能完全解释 MNP 成熟的差异。I 型干扰素（IFN）加速了 MNP 的成熟，但 IFN 信号不是生理刺激。相反，滤泡相关上皮（FAE）M 细胞分化是驱动产后 PP MNP 成熟所必需和充分的。总之，我们的研究结果强调了 FAE M 细胞分化和 MNP 成熟在出生后免疫发育中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/9b6f3312e1b2/gr7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/f9f5b4ec6472/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/89078ea4a254/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/52493be2cd7a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/ceec73578d44/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/9b6f3312e1b2/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/90e4053bc847/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/8a7b5a7867ce/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/dd0191d7ff4c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/f9f5b4ec6472/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/89078ea4a254/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/52493be2cd7a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fbd/10262694/ceec73578d44/gr6.jpg
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