氧气调控免疫反应的塑性：生理氧合与病理性低氧的新兴作用
How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia
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影响因子:60.9
分区:医学1区 Top / 免疫学1区
发表日期:2025 Mar
作者:
Ananda Shanti Mirchandani, Manuel Alejandro Sanchez-Garcia, Sarah Ruth Walmsley
DOI:
10.1038/s41577-024-01087-5
摘要
大部分真核生物都依赖氧气存活，随着多细胞结构的复杂化，组织中的氧气供应和输送速率存在差异。在人类中，健康组织的氧气梯度显著不同，从骨髓（血液造血干细胞所在的低氧环境）到肺部及其肺泡，后者是身体中氧气最丰富的区域。因此，免疫细胞在从骨髓迁移到外围器官发挥效应时，必须适应不同的氧气供应。这些氧气梯度在炎症过程中会被放大，因组织灌流变化和细胞活性增加而导致氧合不足。因此，研究氧合对组织稳态和疾病状态下免疫反应的影响具有重要意义。在本文中，我们讨论了生理氧合（physioxia）和疾病相关低氧（细胞氧需求超过供应）对免疫细胞功能的相关性，探讨了低氧在组织稳态、炎症、感染、癌症以及疾病免疫治疗中的作用。
Abstract
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.