Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in dendritic cells (NF-κB signaling in DCs)

The NF-κB signaling pathway in dendritic cells (DCs) is a fundamental regulator of immune homeostasis and activation, orchestrating the maturation of DCs and their ability to prime T cell responses [1, 12]. It consists of two main branches: the canonical pathway, typically involving p50/RelA heterodimers, and the non-canonical pathway, which utilizes p52/RelB dimers [1, 14]. Activation of these pathways leads to the upregulation of major histocompatibility complex (MHC) molecules, costimulatory receptors such as CD80 and CD86, and the secretion of pro-inflammatory cytokines like IL-12 and TNF-α [4, 11]. In disease states, excessive NF-κB activity in DCs contributes to chronic inflammation and autoimmune disorders, while its suppression can lead to immune tolerance or evasion in the tumor microenvironment [2, 13]. Consequently, the pathway is a major therapeutic target; inhibitors like bortezomib or aspirin are explored to treat inflammatory conditions, while agonists such as F1929-1458 are investigated to stimulate anti-tumor immunity [7, 8, 16]. However, the broad physiological roles of NF-κB pose significant challenges for drug development, as systemic modulation often results in severe on-target toxicities and immunosuppression [14, 17].

Other names

NF-kappaB signaling in dendritic cellsNF-kB pathway in DCsDendritic cell NF-kappaB activationCanonical and non-canonical NF-κB pathways in DCs

Modulation of NF-κB signaling through the inhibition of IκB kinase (IKK) complexes, prevention of IκB degradation via proteasome inhibition, or direct activation of NF-κB subunits to promote dendritic cell maturation and antigen presentation [14, 17].