Nour Eddine Hassan F, Kassem Aya M, Salhab Zahraa, Sherri Nour, Moghabghab Karen, Mohsen Zahraa, Naim Georges, Mahmoud Sally, Jurjus Abdo, Hashash Jana G, Rahal Elias A
Department of Experimental Pathology, Immunology, and Microbiology, American University of Beirut, Beirut 1107-2020, Lebanon.
Center for Infectious Diseases Research (CIDR), American University of Beirut, Beirut 1107, Lebanon.
Biomedicines. 2025 Jun 24;13(7):1535. doi: 10.3390/biomedicines13071535.
: Inflammatory bowel disease (IBD) is a chronic inflammatory condition encompassing ulcerative colitis (UC) and Crohn's disease (CD). The role of environmental factors in the pathogenesis of IBD remains elusive. Nevertheless, evidence suggests a pivotal role of viruses, specifically Epstein-Barr virus (EBV), in the progression of IBD through mechanisms such as molecular mimicry and bystander activation. Our previous findings demonstrate EBV DNA's significant role in exacerbating colitis symptoms and elevating the levels of the pro-autoimmune cytokine interleukin-17A (IL-17A) in an IBD mouse model via toll-like receptor 9 (TLR9). Therefore, we aimed to examine the role of EBV particles in the pathogenesis of IBD, and the potential role of TLR9 inhibition in ameliorating disease outcomes. : Three days post colitis induction, EBV particles were intra-rectally injected into female C57BL/6J mice, followed by the intra-peritoneal administration of TLR9 inhibitor. Thereupon, mice were monitored daily and the disease activity index (DAI), colon lengths, and damage scores, as well as the number of cells, double-positive for IL-17A+ and IFN-γ+, and triple-positive for IL-17A+, IFN-γ+, and FOXP3+, were evaluated. : Our findings revealed a significant role of TLR9 inhibition in mitigating colitis features in an EBV-injected IBD mouse model compared to the control group. : These results indicate an essential role of TLR9 in initiating immune responses against recurrent EBV reactivation events, which ultimately contributes to inflammation aggravation in IBD patients. Consequently, TLR9 could serve as a potential therapeutic target to alleviate the severe symptoms of IBD in EBV-infected individuals.
炎症性肠病（IBD）是一种慢性炎症性疾病，包括溃疡性结肠炎（UC）和克罗恩病（CD）。环境因素在IBD发病机制中的作用仍不明确。然而，有证据表明病毒，特别是爱泼斯坦-巴尔病毒（EBV），通过分子模拟和旁观者激活等机制在IBD进展中起关键作用。我们之前的研究结果表明，在IBD小鼠模型中，EBV DNA通过Toll样受体9（TLR9）在加重结肠炎症状和提高促自身免疫细胞因子白细胞介素-17A（IL-17A）水平方面发挥重要作用。因此，我们旨在研究EBV颗粒在IBD发病机制中的作用，以及TLR9抑制在改善疾病结局方面的潜在作用。：在诱导结肠炎三天后，将EBV颗粒经直肠注射到雌性C57BL/6J小鼠体内，随后腹腔注射TLR9抑制剂。随即，每天对小鼠进行监测，并评估疾病活动指数（DAI）、结肠长度和损伤评分，以及IL-17A+和IFN-γ+双阳性、IL-17A+、IFN-γ+和FOXP3+三阳性的细胞数量。：我们的研究结果显示，与对照组相比，在注射EBV的IBD小鼠模型中，TLR9抑制在减轻结肠炎特征方面发挥了重要作用。：这些结果表明，TLR9在引发针对复发性EBV再激活事件的免疫反应中起重要作用，这最终导致IBD患者炎症加重。因此，TLR9可作为缓解EBV感染个体IBD严重症状的潜在治疗靶点。
