Differential expression of Rel/NF-κB and octamer factors is a hallmark of the generation and maturation of dendritic cells

Abstract

A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-κB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-κB factors did not correlate with lower levels of cytosolic NF-κB inhibitors, the IκBs. One IκB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)

Transcript profiling of human dendritic cells maturation‐induced under defined culture conditions: comparison of the effects of tumour necrosis factor alpha, soluble CD40 ligand trimer and interferon gamma

“…Cluster analysis further showed that maturation-induced DCs (G4T and G4CD40L) had increased expression of helix±loop± helix id2, c-rel, IRF-4, HOX-5 and BTG-1 transcription factors. Our observation of increased c-rel expression following maturation induction confirms a previous study of human dendritic cells (Neumann et al, 2000).…”

Production of IL-12 and IL-18 in human dendritic cells upon infection byListeria monocytogenes

“…A variety of microbial ligands have been shown to activate immune responses via mammalian Toll-like receptors (TLRs) [21]. Monocyte-derived DCs express TLR 1,2,4,5,8 [22]. Several groups have shown that preparations of Gram-positive bacteria mediate cellular signaling via TLR2.…”

The Duality of Fgl2 - Secreted Immune Checkpoint Regulator Versus Membrane-Associated Procoagulant: Therapeutic Potential and Implications

“…In the case of Fgl2-induced inhibition of DC and B cell functions, FcγRIIB phosphorylation was not observed, suggesting that the signaling is triggered in an ITIMindependent manner (46). As an alternative, soluble Fgl2 could block NF-κB translocation into nucleus, resulting in the down-regulation of CD80 and MHC II expression on DCs (13) and likely their maturation (52,53). Finally, data is emerging that shows that Fgl2 regulates adaptive immunity via Th1 and Th2 cytokines.…”