Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Yasmin, N; Bauer, T; Modak, M; Wagner, K; Schuster, C; Köffel, R; Seyerl, M; Stöckl, J; Elbe-Bürger, A; Graf, D; Strobl, H.
Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation.
J Exp Med. 2013; 210(12):2597-2610
Doi: 10.1084/jem.20130275
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- Führende Autor*innen der Med Uni Graz
- Strobl Herbert
- Co-Autor*innen der Med Uni Graz
- Bauer Thomas
- Köffel René
- Wagner Karin
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- Abstract:
- Human Langerhans cell (LC) precursors populate the epidermis early during prenatal development and thereafter undergo massive proliferation. The prototypic antiproliferative cytokine TGF-β1 is required for LC differentiation from human CD34(+) hematopoietic progenitor cells and blood monocytes in vitro. Similarly, TGF-β1 deficiency results in LC loss in vivo. However, immunohistology studies revealed that human LC niches in early prenatal epidermis and adult basal (germinal) keratinocyte layers lack detectable TGF-β1. Here we demonstrated that these LC niches express high levels of bone morphogenetic protein 7 (BMP7) and that Bmp7-deficient mice exhibit substantially diminished LC numbers, with the remaining cells appearing less dendritic. BMP7 induces LC differentiation and proliferation by activating the BMP type-I receptor ALK3 in the absence of canonical TGF-β1-ALK5 signaling. Conversely, TGF-β1-induced in vitro LC differentiation is mediated via ALK3; however, co-induction of ALK5 diminished TGF-β1-driven LC generation. Therefore, selective ALK3 signaling by BMP7 promotes high LC yields. Within epidermis, BMP7 shows an inverse expression pattern relative to TGF-β1, the latter induced in suprabasal layers and up-regulated in outer layers. We observed that TGF-β1 inhibits microbial activation of BMP7-generated LCs. Therefore, TGF-β1 in suprabasal/outer epidermal layers might inhibit LC activation, resulting in LC network maintenance.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bone Morphogenetic Protein 7 - deficiency
- Bone Morphogenetic Protein Receptors, Type I - metabolism
- Cell Differentiation - physiology
- Cells, Cultured -
- Cytokines - biosynthesis
- Epidermis - cytology
- Gene Expression -
- Humans -
- Langerhans Cells - cytology
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Mice, Transgenic -
- Signal Transduction -
- Smad Proteins - metabolism
- Transforming Growth Factor beta1 - physiology