Institute for Genetics, University of Cologne, Cologne, Germany.
Immunol Rev. 2012 Mar;246(1):346-58. doi: 10.1111/j.1600-065X.2012.01109.x.
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.
自发现以来，核因子-κB（NF-κB）一直被认为是免疫反应的关键调节因子。虽然早期的研究集中在研究 NF-κB 在免疫细胞的发育和功能中的作用，但最近抑制 NF-κB 激酶（IKK）/NF-κB 途径的功能在非免疫细胞中受到了更多的关注。遗传小鼠模型的研究对于剖析 NF-κB 的细胞特异性功能至关重要，并提供了实验证据，表明上皮细胞中的 NF-κB 信号对于维持皮肤和肠道等屏障组织中的免疫稳态很重要。IKK/NF-κB 的过度激活会导致上皮细胞表达细胞因子，从而导致组织炎症反应加剧。角质形成细胞中 NF-κB 的抑制会引发严重依赖肿瘤坏死因子的皮肤炎症和表皮增生，而肠上皮细胞中 IKK/NF-κB 信号的抑制会扰乱肠道屏障并引发严重的慢性结肠炎炎症。因此，上皮 NF-κB 信号通过调节细胞存活、屏障完整性以及上皮细胞的免疫和抗微生物反应，在上皮组织与环境的界面处执行关键的“维和”功能。对上皮 NF-κB 功能的深入了解可能是阐明上皮组织慢性炎症性疾病的病因和发病机制的关键。
