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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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IMMUNOBIOLOGY

RelB regulates human dendritic cell subset development by promoting monocyte intermediates

Barbara Platzer, Almut Jörgl, Sabine Taschner, Bernhard Höcher, and Herbert Strobl

From the Institute of Immunology, University of Vienna, Austria.

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-{kappa}B (NF-{kappa}B) 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 p100{Delta}N) blocked, precursor cell development along this DC subset pathway. RelB inhibition specifically arrested precursor progression from CD14loCD11b- 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-{kappa}B signaling inhibition because I{kappa}B{alpha} superrepressor (I{kappa}B{alpha}-SR), but not p100{Delta}N, 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.


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