Chen Yuling, Gaber Timo
Charité-Universitätsmedizin Berlin, Corporate Ember of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, Charitéplatz 1, 10117 Berlin, Germany.
German Rheumatism Research Centre (DRFZ) Berlin, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Biomedicines. 2021 Mar 5;9(3):260. doi: 10.3390/biomedicines9030260.
Oxygen availability varies throughout the human body in health and disease. Under physiological conditions, oxygen availability drops from the lungs over the blood stream towards the different tissues into the cells and the mitochondrial cavities leading to physiological low oxygen conditions or physiological hypoxia in all organs including primary lymphoid organs. Moreover, immune cells travel throughout the body searching for damaged cells and foreign antigens facing a variety of oxygen levels. Consequently, physiological hypoxia impacts immune cell function finally controlling innate and adaptive immune response mainly by transcriptional regulation via hypoxia-inducible factors (HIFs). Under pathophysiological conditions such as found in inflammation, injury, infection, ischemia and cancer, severe hypoxia can alter immune cells leading to dysfunctional immune response finally leading to tissue damage, cancer progression and autoimmunity. Here we summarize the effects of physiological and pathophysiological hypoxia on innate and adaptive immune activity, we provide an overview on the control of immune response by cellular hypoxia-induced pathways with focus on the role of HIFs and discuss the opportunity to target hypoxia-sensitive pathways for the treatment of cancer and autoimmunity.
在健康和疾病状态下，人体各部位的氧气供应情况各不相同。在生理条件下，从肺部到血流，再到不同组织直至细胞和线粒体腔，氧气供应逐渐减少，导致包括初级淋巴器官在内的所有器官都处于生理性低氧状态或生理性缺氧。此外，免疫细胞在全身游走，寻找受损细胞和外来抗原，会面临各种不同的氧气水平。因此，生理性缺氧会影响免疫细胞功能，最终主要通过缺氧诱导因子（HIFs）的转录调控来控制先天性和适应性免疫反应。在诸如炎症、损伤、感染、缺血和癌症等病理生理条件下，严重缺氧会改变免疫细胞，导致免疫反应功能失调，最终导致组织损伤、癌症进展和自身免疫。在此，我们总结生理性和病理性缺氧对先天性和适应性免疫活性的影响，概述细胞缺氧诱导途径对免疫反应的控制，重点关注HIFs的作用，并讨论针对缺氧敏感途径治疗癌症和自身免疫的机会。
