The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece.
Nat Rev Immunol. 2021 Nov;21(11):704-717. doi: 10.1038/s41577-021-00540-z. Epub 2021 Apr 28.
In chronic infection, inflammation and cancer, the tissue microenvironment controls how local immune cells behave, with tissue-resident fibroblasts emerging as a key cell type in regulating activation or suppression of an immune response. Fibroblasts are heterogeneous cells, encompassing functionally distinct populations, the phenotypes of which differ according to their tissue of origin and type of inciting disease. Their immunological properties are also diverse, ranging from the maintenance of a potent inflammatory environment in chronic inflammation to promoting immunosuppression in malignancy, and encapsulating and incarcerating infectious agents within tissues. In this Review, we compare the mechanisms by which fibroblasts control local immune responses, as well as the factors regulating their inflammatory and suppressive profiles, in different tissues and pathological settings. This cross-disease perspective highlights the importance of tissue context in determining fibroblast-immune cell interactions, as well as potential therapeutic avenues to exploit this knowledge for the benefit of patients with chronic infection, inflammation and cancer.
在慢性感染、炎症和癌症中，组织微环境控制着局部免疫细胞的行为，组织驻留成纤维细胞作为调节免疫反应激活或抑制的关键细胞类型出现。成纤维细胞是异质性细胞，包含功能不同的群体，其表型根据其组织来源和引发疾病的类型而有所不同。它们的免疫特性也多种多样，从慢性炎症中维持强烈的炎症环境到促进恶性肿瘤中的免疫抑制，以及在组织内包裹和监禁传染性病原体。在这篇综述中，我们比较了成纤维细胞控制局部免疫反应的机制，以及调节其炎症和抑制表型的因素，在不同的组织和病理环境中。这种跨疾病的观点强调了组织背景在确定成纤维细胞-免疫细胞相互作用中的重要性，以及利用这一知识为慢性感染、炎症和癌症患者带来益处的潜在治疗途径。
