Mucosal Langerhans cells (LCs) originate from pre–dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.

黏膜朗格汉斯细胞（LCs）来自树突前细胞和单核细胞。但是，其原位发育所涉及的机制仍不清楚。在这里，我们证明了鼠黏膜LC的分化是一个两步过程。在固有层中，通过BMP7-ALK3发出的信号促进了LC前体向上皮细胞的转运。在上皮细胞内，TGF-β1完成了LC分化，而ALK5对这一过程至关重要。此外，局部微生物群对粘膜LC的发展有重大影响，而LC又可以维持粘膜稳态并防止组织破坏。这些结果揭示了TGF-β1和BMP7在LC分化中的差异性和顺序性作用，并突出了LC与微生物群的密切相互作用。