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.

免疫生态位是免疫活动的焦点部位，可以具有不同的微环境特征。缺氧是生理和病理免疫生态位的一个特征。缺氧对免疫和炎症的影响可能会有所不同，具体取决于给定生态位中发生的微环境和免疫过程。在生理免疫生态位中，如骨髓、淋巴组织、胎盘和肠粘膜，生理性缺氧通过调节免疫细胞增殖、发育和效应功能来控制先天性和适应性免疫，主要是通过缺氧诱导因子（HIF）驱动的转录变化。相比之下，在病理性免疫生态位中，例如肿瘤和慢性炎症、感染或缺血组织，病理性缺氧可以通过免疫细胞失调驱动组织功能障碍和疾病发展。在这里，我们区分生理和病理性缺氧对免疫细胞的影响以及不同免疫生态位中免疫和炎症的后果。此外，我们讨论了针对免疫细胞中缺氧敏感通路治疗炎症性疾病的可能性。