Kromann Emma Højmose, Cearra Ainize Peña, Neves Joana F
Centre for Host Microbiome Interactions, King's College London, London, United Kingdom.
Department of Immunology, Microbiology and Parasitology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Bilbao, Spain.
Clin Exp Immunol. 2024 Sep 16;218(1):28-39. doi: 10.1093/cei/uxad118.
The intestine hosts the largest immune cell compartment in the body as a result of its continuous exposure to exogenous antigens. The intestinal barrier is formed by a single layer of epithelial cells which separate immune cells from the gut lumen. Bidirectional interactions between the epithelium and the immune compartment are critical for maintaining intestinal homeostasis by limiting infection, preventing excessive immune activation, and promoting tissue repair processes. However, our understanding of epithelial-immune interactions incomplete as the complexity of in vivo models can hinder mechanistic studies, cell culture models lack the cellular heterogeneity of the intestine and when established from primary cell can be difficult to maintain. In the last decade, organoids have emerged as a reliable model of the intestine, recapitulating key cellular and architectural features of native tissues. Herein, we provide an overview of how intestinal organoids are being co-cultured with immune cells leading to substantial advances in our understanding of immune-epithelial interactions in the gut. This has enabled new discoveries of the immune contribution to epithelial maintenance and regeneration both in homeostasis and in disease such as chronic inflammation, infection and cancer. Organoids can additionally be used to generate immune cells with a tissue-specific phenotype and to investigate the impact of disease associated risk genes on the intestinal immune environment. Accordingly, this review demonstrates the multitude of applications for intestinal organoids in immunological research and their potential for translational approaches.
由于肠道持续暴露于外源性抗原，它拥有体内最大的免疫细胞区室。肠道屏障由单层上皮细胞形成，这些上皮细胞将免疫细胞与肠腔分隔开来。上皮细胞与免疫区室之间的双向相互作用对于通过限制感染、防止过度免疫激活和促进组织修复过程来维持肠道稳态至关重要。然而，我们对上皮-免疫相互作用的理解并不完整，因为体内模型的复杂性可能会阻碍机制研究，细胞培养模型缺乏肠道的细胞异质性，并且从原代细胞建立时可能难以维持。在过去十年中，类器官已成为一种可靠的肠道模型，概括了天然组织的关键细胞和结构特征。在此，我们概述了肠道类器官如何与免疫细胞共培养，从而在我们对肠道免疫-上皮相互作用的理解方面取得了重大进展。这使得人们在稳态以及慢性炎症、感染和癌症等疾病中，对免疫在上皮维持和再生中的作用有了新的发现。类器官还可用于生成具有组织特异性表型的免疫细胞，并研究疾病相关风险基因对肠道免疫环境的影响。因此，本综述展示了肠道类器官在免疫研究中的众多应用及其在转化研究中的潜力。
