The NF- κB signaling system in the immunopathogenesis of inflammatory bowel disease

Sci Signal. 2024 Jan 9;17(818):eadh1641. doi: 10.1126/scisignal.adh1641. Epub 2024 Jan 9.ABSTRACTInflammatory bowel disease (IBD) is an idiopathic, chronic condition characterized by episodes of inflammation in the gastrointestinal tract. The nuclear factor κB (NF-κB) system describes a family of dimeric transcription factors. Canonical NF-κB signaling is stimulated by and enhances inflammation, whereas noncanonical NF-κB signaling contributes to immune organogenesis. Dysregulation of NF-κB factors drives various inflammatory pathologies, including IBD. Signals from many immune sensors activate NF-κB subunits in the intestine, which maintain an equilibrium between local microbiota and host responses. Genetic association studies of patients with IBD and preclinical mouse models confirm the importance of the NF-κB system in host defense in the gut. Other studies have investigated the roles of these factors in intestinal barrier function and in inflammatory gut pathologies associated with IBD. NF-κB signaling modulates innate and adaptive immune responses and the production of immunoregulatory proteins, anti-inflammatory cytokines, antimicrobial peptides, and other tolerogenic factors in the intestine. Furthermore, genetic studies have revealed critical cell type-specific roles for NF-κB proteins in intestinal immune homeostasis, inflammation, and restitution that contribute to the etiopathology of IBD-associated manifestations. Here, we summarize our knowledge of the r...
Source: Science Signaling - Category: Biomedical Science Authors: Source Type: research