Behcet's Disease (BD) is a multisystem vasculitis characterized by disease alternated with recurrent episodes and remissions, involving genital, oral, ocular uvea, cutaneous, and articular manifestations. The nuclear factor (NF)-κB signaling pathway paly an important role in the BD progression. It encompasses diverse gene, protein, and cellular regulatory mechanisms operating across various levels, alongside microbiological and experimental studies involving animals and cells. At the protein research findings, activation of the NF-κB pathway in BD patients is marked by elevated plasma levels of soluble CD40 ligand, which stimulates neutrophils to release reactive oxygen species and extracellular traps, thereby promoting inflammation. At the cellular research findings, macrophages in BD patients polarize towards classically activated macrophages phenotype through the NF-κB pathway, exacerbating the inflammatory response. The activation of NF-κB is associated with increased expression of anti-apoptotic proteins in T cells, leading to prolonged inflammation. Microbiological investigations reveal that the decreased gut microbiota diversity in BD patients compromises intestinal barrier integrity. NF-κB pathway involvement in regulating neutrophil and type 1 helper T cell (Th) 1/Th17 cell function worsens inflammation. Genetically, BD patients exhibit polymorphisms in immune regulatory genes, which contribute to inflammation through the NF-κB pathway. Mutations in NF-κB-associated genes elevate the risk of BD, while mutations in the endogenous inhibitor A20 lead to abnormal NF-κB activity, sustaining inflammation. Animal experiments and in vitro experiments corroborate the efficacy of NF-κB inhibitors in attenuating inflammation. Targeting upstream inflammatory factors within the NF-κB pathway yields positive outcomes in BD patients. In summary, the NF-κB signaling pathway plays a pivotal role in the development of BD. Developing NF-κB inhibitors may open new avenues for treating BD. Further research is necessary to comprehensively elucidate the precise mechanisms by which NF-κB operates in the pathogenesis of BD, as well as its potential clinical applications in therapy.

Citation： Zheng Chuanzhen, Zhang Xiaomin. Research status and progress of nuclear factor κappa B signaling pathway in Behçet disease. Chinese Journal of Ocular Fundus Diseases, 2023, 39(10): 862-867. doi: 10.3760/cma.j.cn511434-20220523-00318 Copy