Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

Göbel, F; Taschner, S; Jurkin, J; Konradi, S; Vaculik, C; Richter, S; Kneidinger, D; Mühlbacher, C; Bieglmayer, C; Elbe-Bürger, A; Strobl, H.
Reciprocal role of GATA-1 and vitamin D receptor in human myeloid dendritic cell differentiation.
Blood. 2009; 114(18):3813-3821 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Strobl Herbert

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Two major pathways of human myeloid dendritic cell (DC) subset differentiation have previously been delineated. Langerhans cells (LCs) reside in epithelia in the steady state, whereas monocytes can provide dendritic cells (DCs) on demand in response to inflammatory signals. Both DC subset pathways arise from shared CD14+ monocyte precursors, which in turn develop from myeloid committed progenitor cells. However, the underlying hematopoietic mechanisms still remain poorly defined. Here, we demonstrate that the vitamin D(3) receptor (VDR) is induced by transforming growth factor beta1 during LC lineage commitment and exerts a positive role during LC generation. In contrast, VDR is repressed during interleukin-4 (IL-4)-dependent monocyte-derived DC (moDC) differentiation. We identified GATA-1 as a repressor of VDR. GATA-1 is induced by IL-4 in moDCs. Forced inducible expression of GATA-1 mimics IL-4 in redirecting moDC differentiation and vice versa, GATA-1 knockdown arrests moDC differentiation at the monocyte stage. Moreover, ectopic GATA-1 expression stabilizes the moDC phenotype under monocyte-promoting conditions in the presence of vitamin D3 (VD3). In summary, human myeloid DC subset differentiation is inversely regulated by GATA-1 and VDR. GATA-1 mediates the repression of VDR and enables IL-4-dependent moDC differentiation. Conversely, VDR is induced downstream of transforming growth factor beta1 and is functionally involved in promoting LC differentiation.
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Antigens, CD14 -
Cell Differentiation - drug effects Cell Differentiation - immunology
Dendritic Cells - cytology Dendritic Cells - immunology Dendritic Cells - metabolism
GATA1 Transcription Factor - genetics GATA1 Transcription Factor - immunology GATA1 Transcription Factor - metabolism
Gene Knockdown Techniques -
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Interleukin-4 - genetics Interleukin-4 - immunology Interleukin-4 - pharmacology
K562 Cells -
Monocytes - cytology Monocytes - immunology Monocytes - metabolism
Myeloid Progenitor Cells - cytology Myeloid Progenitor Cells - immunology Myeloid Progenitor Cells - metabolism
Receptors, Calcitriol - genetics Receptors, Calcitriol - immunology Receptors, Calcitriol - metabolism
Repressor Proteins - genetics Repressor Proteins - immunology Repressor Proteins - metabolism
Transforming Growth Factor beta1 - genetics Transforming Growth Factor beta1 - immunology Transforming Growth Factor beta1 - pharmacology
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