氧合如何塑造免疫反应：生理学和病理缺氧的新兴作用
How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia
影响因子:60.90000
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
摘要
大多数真核生物都需要氧气才能生存，并且随着多细胞复杂性的增加，氧气的可用性和递送速度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梯度，范围从骨髓的低氧环境（我们的造血干细胞驻留）到肺及其肺泡，这是人体中最氧化的区域之一。因此，当免疫细胞从骨髓转移到周围器官以介导其效应子功能时，需要适应不同的氧气可用性。在炎症期间，这些变化的氧梯度被夸大了，由于组织灌注改变和细胞活性增加，通常会耗尽氧合。因此，重要的是要考虑氧合在组织稳态和疾病状况期间塑造免疫反应的影响。在这篇综述中，我们解决了生理氧合（生理氧）和与疾病相关的缺氧（细胞氧气需求供应量的供应）对于免疫细胞功能的相关性，并讨论了缺氧在组织稳态，炎症，感染，感染，癌症和免疫治疗的环境下免疫反应的相关性。
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.