Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 215, Issue 2, Pages 481-500Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20171508
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Funding
- Israel Science Foundation [766/16]
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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-beta 1 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-beta 1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.
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