The skin comprises tissue macrophages as the most abundant resident immune cell type. Their diverse tasks including resistance against invading pathogens, attraction of bypassing immune cells from vessels, and tissue repair require dynamic specification. Here, we delineated the postnatal development of dermal macrophages and their differentiation into subsets by adapting single-cell transcriptomics, fate mapping, and imaging. Thereby we identified a phenotypically and transcriptionally distinct subset of prenatally seeded dermal macrophages that self-maintained with very low postnatal exchange by hematopoietic stem cells. These macrophages specifically interacted with sensory nerves and surveilled and trimmed the myelin sheath. Overall, resident dermal macrophages contributed to axon sprouting after mechanical injury. In summary, our data show long-lasting functional specification of macrophages in the dermis that is driven by stepwise adaptation to guiding structures and ensures codevelopment of ontogenetically distinct cells within the same compartment.

皮肤包含作为最丰富的常驻免疫细胞类型的组织巨噬细胞。它们的各种任务包括对入侵病原体的抵抗力，从血管吸引旁路免疫细胞的吸引力以及组织修复需要动态规范。在这里，我们通过适应单细胞转录组学，命运图谱和成像，描绘了皮肤巨噬细胞的产后发育及其分化为子集。因此，我们鉴定了造血干细胞在表型和转录上不同的子集，这些子集是由产前接种的真皮巨噬细胞自我维持的，在产后交换时非常低。这些巨噬细胞特异性地与感觉神经相互作用，并监视和修剪髓鞘。总体而言，常驻皮肤巨噬细胞在机械性损伤后促进轴突发芽。总之，