Adult mouse skin dendritic cells

Early life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here we show that this process is controlled by microbial interaction with a specialized subset of antigen presenting cells. More particularly, we identify CD301b+ type 2 conventional dendritic cells (DC) as a subset in neonatal skin specifically capable of uptake, presentation and generation of regulatory T cells (Tregs) to commensal antigens. In early life, CD301b+ DC2 are enriched for programs of phagocytosis and maturation, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic acid-producing enzyme, RALDH2, deletion of which limited commensal-specific Tregs. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early life tolerance at the cutaneous interface. We wanted to analyze by scRNAseq properties of adult skin dendritic cells and transcriptomics to compare to neonatal skin dendritic cells共生细菌于屏障表面的早期免疫耐受建立，对免疫健康具有持久影响，但其具体机制仍不甚明晰。本研究证实，该过程由微生物与一类特化抗原呈递细胞亚群的相互作用所调控。更具体而言，我们鉴定出CD301b阳性2型常规树突状细胞（CD301b+ type 2 conventional dendritic cells, DC）为新生皮肤中的特化亚群，其可特异性摄取共生抗原、呈递该抗原并诱导调节性T细胞（regulatory T cells, Treg）的生成。在生命早期，CD301b+ DC2富集吞噬作用与成熟相关的生物学程序，同时表达耐受相关标志物。在人类与小鼠皮肤中，微生物的摄取进一步强化了这些特征。与成年个体的对应细胞亚群或其他生命早期DC亚群不同，新生小鼠的CD301b+ DC2高表达视黄酸合成酶RALDH2；敲除该酶会削弱共生菌特异性Treg的生成。综上，细菌与特化DC亚群之间的协同相互作用，是皮肤界面早期免疫耐受建立的关键支撑机制。本研究拟通过单细胞RNA测序（scRNAseq）分析成年皮肤树突状细胞的相关特性，并借助转录组学手段与新生皮肤树突状细胞进行对比。