Reciprocal role of GATA-1 and vitamin D receptor in human myeloid dendritic cell differentiation
| Autor: | Florian Göbel, Adelheid Elbe-Bürger, Christine Vaculik, Sabine Taschner, Jennifer Jurkin, Sabine Konradi, Susanne Richter, Herbert Strobl, Christina Mühlbacher, Doris Kneidinger, Christian Bieglmayer |
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| Rok vydání: | 2009 |
| Předmět: |
Myeloid dendritic cell differentiation
Cellular differentiation CD14 Immunology Lipopolysaccharide Receptors Biology Biochemistry Calcitriol receptor Monocytes Transforming Growth Factor beta1 medicine Humans GATA1 Transcription Factor Myeloid Progenitor Cells U937 cell Monocyte Cell Differentiation Dendritic Cells U937 Cells Cell Biology Hematology Dendritic cell Cell biology Repressor Proteins medicine.anatomical_structure Vitamin D3 Receptor Gene Knockdown Techniques Receptors Calcitriol Interleukin-4 K562 Cells |
| Zdroj: | Blood. 114:3813-3821 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2009-03-210484 |
| Popis: | 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 D3 receptor (VDR) is induced by transforming growth factor β1 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 β1 and is functionally involved in promoting LC differentiation. |
| Databáze: | OpenAIRE |
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