RelB regulates human dendritic cell subset development by promoting monocyte intermediates

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-κB (NF-κB) 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 p100ΔN) 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-κB signaling inhibition because lκBα superrepressor (lκBα-SR), but not not p100ΔN, 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 Re1B regulates human monopoiesis and monocytederived DC subset development. © 2004 by The American Society of Hematology.