溶质转运体 OCTN1/Slc22a4 影响实验性结肠炎的疾病严重程度和对英夫利西单抗的反应:肠道微生物群和免疫调节的作用

IF 4.5 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Federica Del Chierico, Letizia Masi, Valentina Petito, Valerio Baldelli, Pierluigi Puca, Roberta Benvenuto, Marco Fidaleo, Ivana Palucci, Loris Riccardo Lopetuso, Maria Emiliana Caristo, Cinzia Carrozza, Maria Cristina Giustiniani, Noritaka Nakamichi, Yukio Kato, Lorenza Putignani, Antonio Gasbarrini, Giovambattista Pani, Franco Scaldaferri
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引用次数: 0

摘要

背景:炎症性肠病是一种慢性致残性疾病,病因复杂且多因素,目前仍未完全明了。OCTN1是一种有机阳离子转运体,可在调节炎症反应中发挥作用,该分子的某些基因多态性与炎症性肠病风险的增加有关。到目前为止,有关该分子在预测/调节患者对疗法的反应方面的潜力的信息还很有限。本研究旨在评估 OCTN1 在改变肠道微生物群和粘膜免疫对英夫利昔单抗治疗小鼠结肠炎的反应中的作用:方法:采用右旋糖酐硫酸钠结肠炎模型评估静脉注射英夫利西单抗对ocnt1基因敲除小鼠及其C57BL/6对照组的临床疗效。收集粪便、结肠和肠系膜淋巴结样本,分别评估肠道微生物群组成、组织学和T细胞群的差异:结果:Octn1 -/-影响小鼠结肠炎的微生物群谱,并与更严重的菌群失调有关。英夫利西单抗可缓解结肠炎相关的菌群失调,两种菌株的细菌丰富度和均匀度都有所提高。与野生型相比,octn1-/-小鼠的病情较轻,Treg、T记忆、Th2和Th17细胞的基线比例较高:我们的数据支持用小鼠模型研究 OCTN1 基因对炎症性肠病的影响。结论:我们的数据支持用小鼠模型研究 OCTN1 基因对炎症性肠病的影响,这可能是将这种膜转运体作为炎症性疾病的生物标记物和治疗反应预测因子的第一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Solute Transporter OCTN1/Slc22a4 Affects Disease Severity and Response to Infliximab in Experimental Colitis: Role of Gut Microbiota and Immune Modulation.

Background: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis.

Methods: A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively.

Results: Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells.

Conclusions: Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies.

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来源期刊
Inflammatory Bowel Diseases
Inflammatory Bowel Diseases 医学-胃肠肝病学
CiteScore
9.70
自引率
6.10%
发文量
462
审稿时长
1 months
期刊介绍: Inflammatory Bowel Diseases® supports the mission of the Crohn''s & Colitis Foundation by bringing the most impactful and cutting edge clinical topics and research findings related to inflammatory bowel diseases to clinicians and researchers working in IBD and related fields. The Journal is committed to publishing on innovative topics that influence the future of clinical care, treatment, and research.
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