Role of NK-kB in epithelial biology


Since its discovery, nuclear factor-jB (NF-kB) has been recognized as a critical regulator of immune responses. While early studies focused on studying the role of NF-kB in the development and function of immune cells, more recently the function of the inhibitor of NF-kB kinase (IKK) NF-kB pathway in non-immune cells has gained increased attention. Studies in genetic mouse models were instrumental in dissecting the cell-specific functions of NF-kB and provided experimental evidence that NF-kB 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-kB triggered cytokine expression by the epithelial cells, resulting in exacerbated tissue inflammatory responses. NF-kB inhibition in keratinocytes triggered severe tumor necrosis factordependent skin inflammation and epidermal hyperplasia, while inhibition of IKK NF-kB signaling in intestinal epithelial cells disturbed the intestinal barrier and triggered severe chronic colon inflammation. Therefore, epithelial NF-kB 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-kB functions may hold the key for elucidating the etiology and pathophysiology of chronic inflammatory diseases in epithelial tissues.


Immunol. Rev. (2012) 246(1), 346-358