Regulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseases

The nuclear factor-kappa B (NF-kappa B) signalling pathway regulates immune responses and is implicated in the pathogenesis of many inflammatory diseases. Given the well established pro-inflammatory functions of NF-kappa B, inhibition of this pathway would be expected to have anti-inflammatory effects. However, recent studies in mouse models have led to surprising and provocative results, as NF-kappa B inhibition in epithelial cells resulted in the spontaneous development of severe chronic inflammatory conditions. These findings indicate that NF-kappa B signalling acts in non-immune cells to control the maintenance of tissue immune homeostasis. This Review discusses the mechanisms by which NF-kappa B activity in non-immune cells regulates tissue immune homeostasis and prevents the pathogenesis of inflammatory diseases.