Since its discovery, nuclear factor-κB (NF-κB) has been recognized as a critical regulator of immune responses. While early studies focused on studying the role of NF-κB in the development and function of immune cells, more recently the function of the inhibitor of NF-κB kinase (IKK)/NF-κB pathway in non-immune cells has gained increased attention. Studies in genetic mouse models were instrumental in dissecting the cell-specific functions of NF-κB and provided experimental evidence that NF-κB signaling in epithelial cells is important for the maintenance of immune homeostasis in barrier tissues such as the skin and the intestine. Increased activation of IKK/NF-κB triggered cytokine expression by the epithelial cells, resulting in exacerbated tissue inflammatory responses. NF-κB inhibition in keratinocytes triggered severe tumor necrosis factor-dependent skin inflammation and epidermal hyperplasia, while inhibition of IKK/NF-κB signaling in intestinal epithelial cells disturbed the intestinal barrier and triggered severe chronic colon inflammation. Therefore, epithelial NF-κB signaling performs critical 'peace keeping' functions in barrier tissues at the interface with the environment by regulating cell survival, barrier integrity, and the immunological and anti-microbial responses of epithelial cells. Improved understanding of epithelial NF-κB functions may hold the key for elucidating the etiology and pathophysiology of chronic inflammatory diseases in epithelial tissues.
© 2012 John Wiley & Sons A/S.