Dendritic cell development and survival require distinct NF-kappaB subunits.
Despite the established role of dendritic cells (DCs) in regulating T lymphocyte activation, intracellular mechanisms responsible for controlling DC function are largely undefined. Here, we have studied DCs from mice deficient in the p50, RelA, and cRel subunits of the immunomodulatory NF-kappaB transcription factor. Although DC development and function was normal in mice lacking individual NF-kappaB subunits, development of doubly deficient p50(-/-)RelA(-/-) DCs was significantly impaired. In contrast, DCs from p50(-/-)cRel(-/-) mice developed normally, but CD40L- and TRANCE-induced survival and IL-12 production was abolished. Surprisingly, no significant impairment in MHC and costimulatory molecule expression was seen, despite significantly reduced kappaB site binding activity. These results therefore indicate essential, subunit-specific functions for NF-kappaB proteins in regulating DC development, survival, and cytokine production.
Ouaaz
Fateh
F
Columbia University, Department of Biological Sciences, 1110 Fairchild Center, 1212 Amsterdam Avenue, New York, NY 10027, USA.
Arron
Joseph
J
Zheng
Ye
Y
Choi
Yongwon
Y
Beg
Amer A
AA
D000818:Animals; D023201:CD40 Ligand / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D051996:Transcription Factor RelA
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D020569:Proto-Oncogene Proteins c-rel; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D051996:Transcription Factor RelA; D023201:CD40 Ligand; D018664:Interleukin-12