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Platzer, B; Jörgl, A; Taschner, S; Höcher, B; Strobl, H.
RelB regulates human dendritic cell subset development by promoting monocyte intermediates.
Blood. 2004; 104(12):3655-3663 [OPEN ACCESS]
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Authors Med Uni Graz:
Strobl Herbert
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Abstract:
In humans, epithelial Langerhans cells (LCs) and monocyte-derived/interstitial dendritic cells (DCs) constitute 2 myeloid DC sublineages. Molecular mechanisms involved in their development from common myeloid progenitors remain poorly defined. Here we demonstrate that the nuclear factor-kappaB (NF-kappaB) transcription factor RelB regulates the generation of monocytic CD14(+)CD11b(+) precursors of interstitial DCs from human hematopoietic progenitors. RelB overexpression promoted, whereas endogenous RelB inhibition (by p100DeltaN) blocked, precursor cell development along this DC subset pathway. RelB inhibition specifically arrested precursor progression from CD14(lo)CD11b(-) to CD14(+)CD11b(+) stages. Precursors were still capable of LC and granulocyte differentiation but were defective in macrophage-colony-stimulating factor (M-CSF)-dependent monocyte/macrophage differentiation. RelB inhibition markedly differed from classical NF-kappaB signaling inhibition because IkappaBalpha superrepressor (IkappaBalpha-SR), but not p100DeltaN, impaired LC/DC differentiation, DC adhesion, and progenitor cell proliferation. Although RelB up-regulation and nuclear translocation are regarded as hallmarks of human myeloid DC maturation, ectopic RelB overexpression failed to promote DC maturation. Our results suggest that RelB regulates human monopoiesis and monocyte-derived DC subset development.
Find related publications in this database (using NLM MeSH Indexing)
Cell Adhesion -
Cell Differentiation -
Cell Lineage -
Cell Proliferation -
Dendritic Cells - cytology
Hematopoietic Stem Cells - cytology
Humans -
I-kappa B Proteins - pharmacology
Monocytes - cytology
Myeloid Progenitor Cells - cytology
Proto-Oncogene Proteins - physiology
Transcription Factor RelB -
Transcription Factors - physiology

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