Primary Bile Acid Shapes Peripheral Immunity in Inflammatory Bowel Disease-associated Primary Sclerosing Cholangitis.

IF 6.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
André Santos, David Pires, Vanda Marques, Nicole Alesina, Elisa Herraez, Pavel Roudnický, Pedro Rodrigues, Ana Godinho-Santos, Ana Bravo, Catarina Gouveia, Susana Saraiva, Luís Correia, Ricardo Crespo, João da Silva, Marília Cravo, David Potesil, Zbyněk Zdráhal, Jesus Banales, Jose Marin, Joana Torres, Cecília Rodrigues
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引用次数: 0

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with underlying inflammatory bowel disease (IBD). This study investigates how PSC predisposes altered inflammatory immune responses and compared to IBD alone. A case-control study was conducted with a cohort of 75 patients, including 16 with PSC (14 with concomitant IBD), 39 with IBD alone, and 20 controls. Serum bile acid profile, proteomic analysis, and immune-related gene expression in colon tissue were examined. Colonic tissue from PSC patients exhibited upregulation of immune regulation and inflammatory signaling mRNA markers, including LGR5, IL-8, CCL2, COX2, TWIST1, and SNAIL. Additionally, PSC patients displayed a distinct proinflammatory serum proteomic signature and moderate elevation of some bile acids, such as glycochenodeoxycholic acid (GCDCA). Co-incubation of human-derived monocytes with GCDCA partially replicated the inflammatory profile observed in PSC. These findings suggest that circulating bile acids modulate peripheral immune system proinflammatory response, contributing to the unique PSC phenotype.

原发性胆汁酸影响炎症性肠病相关原发性硬化性胆管炎的外周免疫
原发性硬化性胆管炎(PSC)是一种慢性胆汁淤积性肝病,常与潜在的炎症性肠病(IBD)相关。本研究探讨了PSC如何易感改变炎症免疫反应,并与IBD单独比较。一项病例对照研究对75名患者进行了队列研究,包括16名PSC患者(14名合并IBD), 39名单独IBD患者和20名对照组。检测血清胆汁酸谱、蛋白质组学分析和结肠组织免疫相关基因表达。PSC患者结肠组织显示免疫调节和炎症信号mRNA标志物上调,包括LGR5、IL-8、CCL2、COX2、TWIST1和SNAIL。此外,PSC患者表现出明显的促炎血清蛋白质组学特征和一些胆汁酸(如糖鹅脱氧胆酸(GCDCA))的中度升高。人源性单核细胞与GCDCA共孵育部分复制了PSC中观察到的炎症特征。这些发现表明,循环胆汁酸调节外周免疫系统的促炎反应,有助于独特的PSC表型。
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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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