RelB regulates human dendritic cell subset development by promoting monocyte intermediates

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 ReIB regulates the generation of monocytic CD14(+)CD11b(+) precursors of interstitial DCs from human hematopoietic progenitors. ReIB overexpression promoted, whereas endogenous ReIB inhibition (by p100DeltaN) blocked, precursor cell development along this DC subset pathway. ReIB inhibition specifically arrested precursor progression from CD14(lo)CD11(-) 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. ReIB 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 ReIB up-regulation and nuclear translocation are regarded as hallmarks of human myeloid DC maturation, ectopic ReIB overexpression failed to promote DC maturation. Our results suggest that ReIB regulates human monopoiesis and monocyte-derived DC subset development. (C) 2004 by The American Society of Hematology.