Most eukaryotes require oxygen for their survival and, with increasing multicellular complexity, oxygen availability and delivery rates vary across the tissues of complex organisms. In humans, healthy tissues have markedly different oxygen gradients, ranging from the hypoxic environment of the bone marrow (where our haematopoietic stem cells reside) to the lungs and their alveoli, which are among the most oxygenated areas of the body. Immune cells are therefore required to adapt to varying oxygen availability as they move from the bone marrow to peripheral organs to mediate their effector functions. These changing oxygen gradients are exaggerated during inflammation, where oxygenation is often depleted owing to alterations in tissue perfusion and increased cellular activity. As such, it is important to consider the effects of oxygenation on shaping the immune response during tissue homeostasis and disease conditions. In this Review, we address the relevance of both physiological oxygenation (physioxia) and disease-associated hypoxia (where cellular oxygen demand outstrips supply) for immune cell functions, discussing the relevance of hypoxia for immune responses in the settings of tissue homeostasis, inflammation, infection, cancer and disease immunotherapy.

大多数真核生物的生存需要氧气，并且随着多细胞复杂性的增加，氧气的可用性和输送率在复杂生物体的组织中各不相同。在人类中，健康组织具有明显不同的氧气梯度，从骨髓（我们的造血干细胞所在的地方）的缺氧环境到肺部及其肺泡，这是身体含氧量最高的区域之一。因此，当免疫细胞从骨髓移动到外周器官以调节其效应功能时，它们需要适应不同的氧气供应。这些变化的氧梯度在炎症过程中被夸大，由于组织灌注的改变和细胞活动的增加，氧合常常被耗尽。因此，重要的是要考虑氧合对组织稳态和疾病条件下免疫反应的影响。在这篇综述中，我们讨论了生理氧合（生理氧）和疾病相关缺氧（细胞氧需求超过供应）与免疫细胞功能的相关性，讨论了组织稳态、炎症、免疫反应等情况下缺氧与免疫反应的相关性。感染、癌症和疾病免疫治疗。