Gastrointestinal Unit, Third Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece.
Departments of Pathology and Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Inflamm Bowel Dis. 2022 Mar 2;28(3):337-349. doi: 10.1093/ibd/izab251.
Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn's disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.
肠纤维化是炎症性肠病（IBD）的晚期表型，是患者发生大多数长期并发症和手术干预的基础，尤其是克罗恩病患者。尽管存在这些问题，但抗纤维化疗法仍然很少，主要是因为目前对介导慢性肠道炎症患者纤维化发生的发病机制缺乏了解。在本次综述中，我们总结了关于先天和适应性免疫的细胞和分子因素的最新证据，这些因素被认为对细胞外基质沉积和狭窄形成的启动和放大至关重要。我们重点讨论了细胞因子的作用，通过剖析免疫反应的促纤维化和抗纤维化成分，并考虑到它们与 IBD 自然病史的渐进阶段的时间关联。我们从肠道纤维化的动物模型中批判性地呈现证据，并分析在这种实验情况下发生的炎症-纤维化相互作用。此外，我们还对 IBD 患者中与纤维化相关的群体进行的大规模单细胞分析的最新发现进行了评论。基于这些证据，我们提出了未来治疗 IBD 患者的抗纤维化治疗的潜在靶点。
