Background

Classical and novel IKK/NF-κB signaling pathway
Classical and novel IKK/NF-κB signaling pathway

The immune system constitutes the main defensive line against microbial pathogens, e.g. bacteria, viruses or fungi. The immune response can be divided into two principal systems. The early innate system depends on the recognition of ancestral bacterial, viral or fungal structures by invariant pattern recognition receptors, but many pathogens escape the innate immune response. Specific recognition of pathogen-derived antigens is a unique feature of the late adaptive immunity, which is based on clonal selection of lymphocytes bearing antigen receptors (AR). In addition, the development of immunological memory by cells of the adaptive immune response provides enhanced protection against re-infection.

Binding of pathogenic agents to immune cell receptors initiates the activation of cellular signaling pathways and a nuclear transcription program. A central regulator of innate and adaptive immune responses triggered by cytokines, pathogens and antigenic peptides is the IκB kinase (IKK)/NF-κB (Nuclear factor-kappa B) signaling pathway. By orchestrating target gene expression, NF-κB transcription factors promote a cellular reprogramming and induce survival, proliferation and/or differentiation of immune cells. Deregulations in the IKK/NF-κB signaling pathways are associated with human diseases, such as chronic inflammation, autoimmunity and tumor development.