Role of NF-κB activation in intestinal immune homeostasis

Inflammatory bowel diseases (IBD) are characterised by a disturbance of intestinal immune homeostasis, either caused by or followed by inappropriate responses to the resident commensal bacteria. Although the transcription factor NF-κB actively participates in the excessive inflammatory response observed in IBD, recent studies with mice defective in NF-κB activation have revealed that NF-κB also serves an essential protective function in the intestinal immune system. The enormous amount of commensal bacteria in the intestine might play a role in the distinct functions of NF-κB in the intestine, as they can initiate signalling to NF-κB through both Toll-like receptors and NOD-like receptors in intestinal epithelial cells as well as mucosal immune cells. However, the exact individual contributions of different NF-κB-activating stimuli as well as the target cells that mediate the detrimental or beneficial functions of NF-κB in the intestine are still elusive. In this review, I will summarise and discuss the current knowledge on the role of different NF-κB-activating pathways in preserving intestinal immune homeostasis and the development of intestinal inflammation.