Regulation of Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κβ) in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD), encompassing both Crohn Disease (CD) and ulcerative colitis (UC) are globally prevalent diseases, impacting children of all ages. The hallmark of IBD is a perturbed immune system that leads to continuous inflammation in the gut and challenges optimal treatment. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), a nuclear transcription factor, plays a major role in gut homeostasis and contributes significantly toward a balanced, homeostatic immune system. Dysregulation in the NF-κβ pathway and factors that regulate it lead to a state of uncontrolled inflammation and altered immunity, as typically observed in IBD. Levels of proinflammatory cytokines that are regulated through NF-κβ are increased in both CD and UC. Genes known to activate NF-κβ, such as, Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Interleukin 23 (IL-23), are associated with IBD. Factors involved in inhibition of NF-κβ, such as A20 and TOLLIP, are also affected in IBD, resulting in failed inflammation suppression/regulation. NOD-2 and A20 have specifically been found to be strongly associated with pediatric IBD. Gut commensals are known to exert anti-inflammatory activities toward NF-κβ and can have a potential role in attenuating inflammation that likely occurs due to microbial dysbiosis in IBD. Failure to terminate/downregulate NF-κβ signaling results in chronic inflammation in IBD. Well-regulated control of inflammation in children with IBD can help better control the disease and suppress immune responses. Better understanding of factors that control NF-κβ can potentially lead toward discovering targeted therapeutic interventions for IBD. Suppression of NF-κβ can be achieved through many modalities including anti-sense oligonucleotides (ASOs), siRNA (small interfering RNA), factors regulating NF-κβ, and microbes. This review focuses on the role of NF-κβ, especially in pediatric IBD, and potential therapeutic venues for attenuating NF-κβ-induced inflammation.