Role of NF‐κB in epithelial biology

Summary:  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.