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:
早期免疫发育对长期宿主健康至关重要。然而,决定出生后免疫成熟速度的机制尚未完全解决.这里,我们分析了小肠Peyer斑块(PPs)中的单核吞噬细胞(MNPs),肠道免疫的主要诱导部位。常规1型和2型树突状细胞(cDC1和cDC2)和RORgt+抗原呈递细胞(RORgt+APC)在亚群组成上表现出显著的年龄依赖性变化,组织分布,减少细胞成熟,随后导致出生后缺乏CD4+T细胞启动。微生物线索有助于但不能完全解释MNP成熟的差异。I型干扰素(IFN)加速MNP成熟,但IFN信号传导不代表生理刺激。相反,卵泡相关上皮(FAE)M细胞分化是必需的,并且足以驱动断奶后PPMNP成熟。一起,我们的结果强调了FAEM细胞分化和MNP成熟在出生后免疫发育中的作用.