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淋巴系统在炎症性肠病发病机制和治疗中的作用。

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease.

机构信息

Department of Gastroenterology, Amsterdam Institute for Gastroenterology Endocrinology and Metabolism, Academic Medical Center, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology & Immunology Center (ARC), Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

出版信息

Int J Mol Sci. 2022 Feb 6;23(3):1854. doi: 10.3390/ijms23031854.

Abstract

Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of the disease's etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer's patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.

摘要

尽管近年来治疗炎症性肠病 (IBD) 的治疗选择有所增加,但由于对现有治疗方法无反应或失去反应,患者的生活质量下降。对疾病病因的深入了解可以为 IBD 的治疗策略提供新的见解。淋巴系统成分通常与免疫反应有关,推测与炎症性疾病的病理生理学有关。本综述旨在总结与 IBD 发病机制相关的淋巴组织中免疫介导的机制的发现,以及(潜在)新的治疗方法。在 IBD 患者和动物模型中,观察到肠系膜淋巴结 (MLN) 和其他淋巴样结构(如派尔集合淋巴结)中的先天和适应性免疫反应增强。此外,MLN 和淋巴管中以肉芽肿形式出现的淋巴阻塞现象与疾病活动度相关。有证据表明,淋巴间质成分和淋巴结微生物组的异常在 IBD 中很常见,并且可以在治疗上加以利用。最后,靶向淋巴细胞迁移的新型药物已被添加到 IBD 的治疗武器库中。总的来说,肠道相关淋巴组织在 IBD 的免疫发病机制中起着关键作用,这可能提供新的治疗靶点。

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