Taylor Cormac T, Colgan Sean P
UCD Conway Institute, Systems Biology Ireland and the School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, 80045 Colorado, USA.
Nat Rev Immunol. 2017 Dec;17(12):774-785. doi: 10.1038/nri.2017.103. Epub 2017 Oct 3.
Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.
免疫微环境是具有不同微环境特征的免疫活动焦点部位。缺氧是生理和病理免疫微环境的一个特征。缺氧对免疫和炎症的影响可能因特定微环境中发生的微环境和免疫过程而异。在生理免疫微环境中，如骨髓、淋巴组织、胎盘和肠道黏膜，生理性缺氧主要通过缺氧诱导因子（HIF）驱动的转录变化来调节免疫细胞增殖、发育和效应功能，从而控制先天性和适应性免疫。相比之下，在病理免疫微环境中，如肿瘤以及慢性炎症、感染或缺血组织，病理性缺氧可通过免疫细胞失调导致组织功能障碍和疾病发展。在这里，我们区分了生理性和病理性缺氧对免疫细胞的影响以及对不同免疫微环境中免疫和炎症的后果。此外，我们还讨论了针对免疫细胞中缺氧敏感途径治疗炎症性疾病的可能性。
