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干扰素调节因子5:溃疡性结肠炎中的一种新型炎症标志物及有前景的治疗靶点

Interferon Regulator Factor 5: A Novel Inflammatory Marker and Promising Therapeutic Target in Ulcerative Colitis.

作者信息

Farrag Karima, Aksan Aysegül, Korotkova Marina, Idborg Helena, Jakobsson Per-Johan, Weigert Andreas, Vieth Michael, Zeuzem Stefan, Blumenstein Irina, Stein Jürgen

机构信息

Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60594 Frankfurt am Main, Germany.

Interdisciplinary Crohn Colitis Centre Rhein-Main, 60594 Frankfurt am Main, Germany.

出版信息

Biomedicines. 2025 Sep 12;13(9):2251. doi: 10.3390/biomedicines13092251.

DOI:10.3390/biomedicines13092251
PMID:41007813
Abstract

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation affecting the gastrointestinal tract and extraintestinal organs. The etiology of IBD is multifactorial, involving genetic, immunological, and environmental factors. Over 200 genetic loci have been associated with the disease, indicating a significant genetic predisposition. Despite advances in understanding its genetic basis, clinical management remains challenging due to heterogeneity in disease presentation and variable treatment responses. Current therapies, such as 5-aminosalicylates and biologics, are not universally effective, underscoring the need for reliable biomarkers to predict therapeutic responses. This study investigates the potential role of interferon regulatory factor 5 (IRF5) in the pathogenesis of IBD, with a particular focus on UC. We conducted a systematic analysis of colon biopsies from 30 adult patients diagnosed with UC and from 8 non-IBD controls. Immunostaining was performed to assess IRF5 expression in colonic tissues using the primary IRF5 antibody (1:300, Abcam, ab181553). Statistical analyses evaluated the correlation between IRF5-positive cell counts, disease activity, and inflammatory markers such as calprotectin. Our analysis revealed a significant increase in IRF5-positive macrophage-like cells in the inflamed mucosa of IBD patients compared to healthy controls. The number of IRF5-positive cells showed a positive correlation with disease activity and calprotectin levels, indicating that higher IRF5 expression is associated with increased inflammation. This study demonstrates a significant correlation between IRF5 expression and disease activity in UC, suggesting that IRF5 may play a crucial role in the inflammatory processes of the disease. The findings propose IRF5 as a novel biomarker for therapeutic intervention in IBD. Further research is needed to clarify the mechanisms by which IRF5 contributes to IBD pathogenesis and to explore the therapeutic potential of targeting this pathway in clinical settings.

摘要

炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),其特征是胃肠道和肠外器官受到慢性炎症影响。IBD的病因是多因素的,涉及遗传、免疫和环境因素。超过200个基因位点与该疾病相关,表明存在显著的遗传易感性。尽管在理解其遗传基础方面取得了进展,但由于疾病表现的异质性和可变的治疗反应,临床管理仍然具有挑战性。目前的疗法,如5-氨基水杨酸酯和生物制剂,并非普遍有效,这突出了需要可靠的生物标志物来预测治疗反应。本研究调查了干扰素调节因子5(IRF5)在IBD发病机制中的潜在作用,尤其关注UC。我们对30名诊断为UC的成年患者和8名非IBD对照的结肠活检组织进行了系统分析。使用抗IRF5一抗(1:300,Abcam,ab181553)进行免疫染色,以评估结肠组织中IRF5的表达。统计分析评估了IRF5阳性细胞计数、疾病活动度和炎症标志物(如钙卫蛋白)之间的相关性。我们的分析显示,与健康对照相比,IBD患者炎症黏膜中IRF5阳性巨噬细胞样细胞显著增加。IRF5阳性细胞数量与疾病活动度和钙卫蛋白水平呈正相关,表明IRF5表达升高与炎症增加相关。本研究表明UC中IRF5表达与疾病活动度之间存在显著相关性,提示IRF5可能在该疾病的炎症过程中起关键作用。这些发现提出IRF5作为IBD治疗干预的一种新型生物标志物。需要进一步研究来阐明IRF5促成IBD发病机制的机制,并探索在临床环境中靶向该途径的治疗潜力。

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