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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3655-3663.
Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-02-0412.


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Submitted February 2, 2004
Accepted July 15, 2004

RelB Regulates Human Dendritic Cell Subset Development by Promoting Monocyte Intermediates

Barbara Platzer, Almut Jorgl, Sabine Taschner, Bernhard Hocher, and Herbert Strobl*

Institute of Immunology, University of Vienna, Vienna, Austria

* Corresponding author; email: herbert.strobl{at}univie.ac.at.

In humans, epithelial Langerhans cells (LCs) and monocyte-derived/interstitial dendritic cells (DCs) constitute two myeloid DC sublineages. Molecular mechanisms involved in their development from common myeloid progenitors remain poorly defined. Here we demonstrate that the NF-{kappa}B transcription factor RelB regulates the generation of monocytic CD14+CD11b+ precursors of interstitial DC from human hematopoietic progenitors. RelB overexpression promoted, whereas inhibition of endogenous RelB (by p100DN) blocked precursor cell development along this DC subset pathway. Inhibition of RelB specifically arrested precursor progression from CD14loCD11b- to CD14+CD11b+ stages. Precursors were still capable of LC and granulocyte differentiation, but defective in macrophage colony-stimulating factor (M-CSF)-dependent monocyte/macrophage differentiation. RelB inhibition furthermore markedly differed from inhibition of classical NF-{kappa}B signaling, since I{kappa}B{alpha}-superrepressor (I{kappa}B{alpha}-SR) but not p100DN impaired both LC/DC differentiation, DC adhesion and progenitor cell proliferation. Furthermore, despite RelB upregulation and nuclear translocation is regarded a hallmark of human myeloid DC maturation, RelB overexpression failed to promote DC maturation. Our results suggest that RelB regulates human monopoiesis and monocyte-derived DC subset development.


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