Nuclear factor kappa B and Extracellular signal-regulated kinase signaling pathway (NF-κB/ERK signaling)

NF-κB/ERK signaling in bone marrow-derived dendritic cells (BMDCs) represents a critical regulatory axis for the maturation and activation of the innate immune system (PubMed: 25633458). NF-κB (Nuclear Factor kappa B) is a transcription factor family essential for the expression of pro-inflammatory cytokines and MHC molecules, while ERK (Extracellular Signal-Regulated Kinase) is a member of the Mitogen-Activated Protein Kinase (MAPK) family that translates extracellular signals into cellular responses such as proliferation and differentiation (UniProt: P19838, P27361). In BMDCs, the integration of these pathways often occurs downstream of Toll-like receptors (TLRs), leading to the production of cytokines like IL-12 and TNF-α, which are vital for T-cell priming (PubMed: 31235045). Dysregulation of this signaling axis is implicated in chronic inflammatory conditions and autoimmune disorders, where overactive BMDCs drive pathological immune responses. Pharmacological modulation of these pathways, through inhibitors of IKK or MEK, aims to dampen excessive inflammation, though such interventions must balance therapeutic efficacy with the risk of broad immunosuppression. This signaling network is also a target in cancer immunotherapy, where enhancing BMDC activation can improve anti-tumor T-cell responses. Overall, the NF-κB/ERK axis serves as a molecular switch determining the immunogenic versus tolerogenic state of dendritic cells.

Other names

NF-kappaB/MAPK signalingNF-kB/ERK pathwayNF-kappaB/ERK signaling in BMDCsNuclear factor-kappa B and Extracellular signal-regulated kinase pathway

Inhibition of the IκB kinase (IKK) complex prevents the phosphorylation and subsequent degradation of IκB, thereby sequestering NF-κB in the cytoplasm and preventing its transcriptional activity. Simultaneously, inhibition of MEK1/2 prevents the phosphorylation and activation of ERK1/2, blocking the MAPK signaling cascade that drives dendritic cell maturation and cytokine production (PubMed: 25633458).