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Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon‐γ‐inducible protein 16 (IFI16) was reported to be involved in the pathogenesis of Behçet's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real‐time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor‐α (TNF‐α) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (P = 0.012). The plasma TNF‐α protein level in intestinal BS was significantly higher than in healthy controls (HCs; P = 0.009). PBMCs of intestinal BS patients and HCs were co‐cultured with human normal IECs (NCM460) to explore the interaction between immunological cells and IECs. Using IFI16 knockdown, PBMC‐NCM460 co‐culture, TNF‐α neutralizing monoclonal antibody (mAb), stimulator of interferon genes (STING) agonist 2′3′‐cGAMP, and the PLK1 inhibitor SBE 13 HCL, we found that PLK1 promotes the secretion of TNF‐α from PBMCs of intestinal BS patients, which causes overexpression of IFI16 and induces apoptosis of IECs via the STING–TBK1 pathway. The expressions of IFI16, TNF‐α, cleaved caspase 3, phosphorylated STING (pSTING) and phosphorylated tank binding kinase 1 (pTBK1) in the intestinal ulcer tissue of BS patients were significantly higher than that of HCs (all P < 0.05). PLK1 in PBMCs of intestinal BS patients increased TNF‐α secretion, inducing IEC apoptosis via activation of the IFI16–STING–TBK1 pathway. PLK1 and the IFI16–STING–TBK1 pathway may be new therapeutic targets for intestinal BS. [ABSTRACT FROM AUTHOR]

Objective: Behçet's syndrome (BS) is a variant vessel vasculitis that can involve multiple organs, with highly heterogeneous clinical manifestations. This study aims to analyze baseline data of BS patients to enhance the comprehension of its clinical features., Methods: This study included 1216 registered cases of BS patients referred to Huadong Hospital affiliated with Fudan University. Each patient was thoroughly assessed and recorded for demographic data, clinical manifestations, gastrointestinal endoscope, imaging, etc. RESULTS: Significant gender differences were observed in clinical manifestations. Pseudofolliculitis (p < .001), uveitis (p = .003), vascular (p < .001), and cardiovascular involvement (p < .001) were significantly more prevalent in male BS patients, while genital ulcers (p = .011) and erythema nodosum (p = .009) were more common among the female. Furthermore, pseudofolliculitis (44.3%, 37.4% vs. 25.0%, p < .001), pathergy test positivity (37.0%, 24.5% vs. 12.6%, p < .001), and uveitis (18.8%, 18.4% vs. 11.2%, p < .001) showed higher incidence rates in the 16-35 years age group. Vascular involvement (11.1%, 18.0% vs. 15.8%, p < .001) notably increased in the 36-50 years age group. Additionally, the ISG diagnostic criteria were more likely to be met in the 16-35 age group (OR: 2.039, 95% CI: 1.581-2.631, p < .001), whereas the ICBD criteria were less likely to be met in the 16-35 age group (OR: 0.266, 95% CI: 0.150-0.474, p < .001)., Conclusions: This study provided data on the baseline of clinical features of BS in a single center, BS patients presented significant heterogeneity, showing different manifestations across various genders and age groups. This diversity might contribute to a better understanding of BS clinical features and pave the way for future multi-center studies., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)