Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation
Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation
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DOI：
10.1136/gutjnl-2012-303955
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发表时间：
2013-11-01
期刊：
影响因子：
24.5
通讯作者：
Kaser, Arthur
中科院分区：
文献类型：
--
作者：
Cader, M. Zaeem;Kaser, Arthur
肠道及其免疫系统已经进化到能够满足维持对最大、最复杂和多样化的微生物共生栖息地的耐受性的非凡任务，同时精心攻击和遏制甚至极少数偶尔传入的病原体。虽然我们的理解还远未完成，但最近的研究为许多不同的肠道免疫细胞类型之间的复杂相互作用以及全新细胞亚群的发现提供了令人兴奋的新见解。这些研究还揭示了肠道免疫系统的正常发育和功能如何依赖于其特定的微生物群，这些微生物群似乎在进化上是共同进化的。在这里，我们回顾了维持肠道稳态的关键免疫细胞，并描述了功能改变和失衡如何导致炎症性肠病 (IBD)。我们重点介绍该领域的最新进展，涵盖 IBD 的主要参与者，包括肠上皮细胞、巨噬细胞、树突状细胞、适应性免疫细胞和新发现的先天淋巴细胞，这些细胞对粘膜表面的免疫功能具有重要的特征。我们将这些粘膜免疫通路置于 IBD 风险基因的功能背景中，这样的洞察力是可用的。此外，我们在针对这些细胞分泌的关键介质的 IBD 临床试验结果的背景下，对模型系统中已阐明的基本生物学途径进行了讨论，作为对人类疾病中这些途径的功能评估的尝试。
The intestine and its immune system have evolved to meet the extraordinary task of maintaining tolerance to the largest, most complex and diverse microbial commensal habitat, while meticulously attacking and containing even minute numbers of occasionally incoming pathogens. While our understanding is still far from complete, recent studies have provided exciting novel insights into the complex interplay of the many distinct intestinal immune cell types as well as the discovery of entirely new cell subsets. These studies have also revealed how proper development and function of the intestinal immune system is dependent on its specific microbiota, which appears to have evolutionarily co-evolved. Here we review key immune cells that maintain intestinal homeostasis and, conversely, describe how altered function and imbalances may lead to inflammatory bowel disease (IBD). We highlight the latest developments within this field, covering the major players in IBD including intestinal epithelial cells, macrophages, dendritic cells, adaptive immune cells, and the newly discovered innate lymphoid cells, which appear of characteristic importance for immune function at mucosal surfaces. We set these mucosal immune pathways in the functional context of IBD risk genes where such insight is available. Moreover, we frame our discussion of fundamental biological pathways that have been elucidated in model systems in the context of results from clinical trials in IBD that targeted key mediators secreted by these cells, as an attempt of functional' appraisal of these pathways in human disease.