Microbiology and Immunology Department, Stanford University School of Medicine, Stanford, CA 94305.
Immunology Program, Stanford University School of Medicine, Stanford, CA 94304.
Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2404927121. doi: 10.1073/pnas.2404927121. Epub 2024 Nov 14.
Current evidence suggests that ontogeny may account for the functional heterogeneity of some tissue macrophages, but not others. Here, we asked whether developmental origin drives different functions of skin Langerhans cells (LCs), an embryo-derived mononuclear phagocyte with features of both tissue macrophages and dendritic cells. Using time-course analyses, bone marrow chimeras, and fate tracing models, we found that the complete elimination of embryo-derived LCs at steady state results in their repopulation from circulating monocytes. However, monocyte-derived LCs inefficiently replenished the epidermal niche. Instead, these cells preferentially migrated to skin-draining lymph nodes. Mechanistically, we show that the enhanced migratory capability of monocyte-derived LCs is associated with higher expression of CD207/Langerin, a C-type lectin involved in the capture of skin microbes. Our data demonstrate that ontogeny plays a role in the migratory behavior of epidermal LCs.
目前的证据表明，个体发生可能是某些组织巨噬细胞功能异质性的原因，但不是其他原因。在这里，我们想知道发育起源是否会驱动皮肤朗格汉斯细胞（LCs）的不同功能，LCs 是一种来源于胚胎的单核吞噬细胞，具有组织巨噬细胞和树突状细胞的特征。我们使用时间过程分析、骨髓嵌合体和命运追踪模型发现，在稳定状态下完全消除胚胎来源的 LCs 会导致它们从循环单核细胞中重新填充。然而，单核细胞来源的 LCs 不能有效地补充表皮龛。相反，这些细胞优先迁移到皮肤引流淋巴结。从机制上讲，我们表明单核细胞来源的 LCs 增强的迁移能力与参与捕获皮肤微生物的 C 型凝集素 CD207/Langerin 的高表达有关。我们的数据表明，个体发生在表皮 LCs 的迁移行为中起作用。
