Abstract
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.
© 2018 Capucha et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Surface / genetics
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Antigens, Surface / metabolism
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Bone Morphogenetic Protein 7 / genetics
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Bone Morphogenetic Protein 7 / immunology*
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Bone Morphogenetic Protein Receptors, Type I / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Humans
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Immunity, Mucosal
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Langerhans Cells / cytology
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Langerhans Cells / immunology*
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Langerhans Cells / metabolism
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Lectins, C-Type / deficiency
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Lectins, C-Type / genetics
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Lectins, C-Type / metabolism
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Male
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Mannose-Binding Lectins / deficiency
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Mannose-Binding Lectins / genetics
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Mannose-Binding Lectins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microbiota / immunology*
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Mouth Mucosa / cytology
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Mouth Mucosa / immunology
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Receptor, Transforming Growth Factor-beta Type I / metabolism
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Signal Transduction / immunology
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Stem Cells / cytology
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Stem Cells / immunology
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Transcriptome
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / immunology*
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Up-Regulation
Substances
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Antigens, Surface
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Bone Morphogenetic Protein 7
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Cd207 protein, mouse
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Lectins, C-Type
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Mannose-Binding Lectins
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Tgfb1 protein, mouse
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Transforming Growth Factor beta1
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bmp7 protein, mouse
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Bmpr1a protein, mouse
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Bone Morphogenetic Protein Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Tgfbr1 protein, mouse