Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.
Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.
复制标题
DOI：
10.1038/s41590-022-01216-z
复制
发表时间：
2022-06
影响因子：
30.5
通讯作者：
Walmsley, Sarah R.
中科院分区：
文献类型：
--
作者：
Mirchandani, Ananda S.;Jenkins, Stephen J.;Bain, Calum C.;Sanchez-Garcia, Manuel A.;Lawson, Hannah;Coelho, Patricia;Murphy, Fiona;Griffith, David M.;Zhang, Ailiang;Morrison, Tyler;Ly, Tony;Arienti, Simone;Sadiku, Pranvera;Watts, Emily R.;Dickinson, Rebecca S.;Reyes, Leila;Cooper, George;Clark, Sarah;Lewis, David;Kelly, Van;Spanos, Christos;Musgrave, Kathryn M.;Delaney, Liam;Harper, Isla;Scott, Jonathan;Parkinson, Nicholas J.;Rostron, Anthony J.;Baillie, J. Kenneth;Clohisey, Sara;Pridans, Clare;Campana, Lara;Lewis, Philip Starkey;Simpson, A. John;Dockrell, David H.;Schwarze, Jurgen;Hirani, Nikhil;Ratcliffe, Peter J.;Pugh, Christopher W.;Kranc, Kamil;Forbes, Stuart J.;Whyte, Moira K. B.;Walmsley, Sarah R.
低氧血症是急性呼吸窘迫综合征（ARDS）的一个定义性特征，ARDS是肺部或全身炎症的一种致命并发症，但由此产生的组织缺氧及其对免疫反应的影响往往被忽视。在本研究中，我们发现ARDS患者在通气的最初48小时内出现低氧血症和单核细胞减少。在缺氧性急性肺损伤的小鼠模型中也观察到单核细胞减少症，其中低氧血症驱动骨髓中I型干扰素信号传导的抑制。这种受损的单细胞生成导致单核细胞衍生的巨噬细胞的积累减少，并增强肺中嗜中性粒细胞介导的炎症。在缺氧性肺损伤小鼠中给予集落刺激因子1可挽救单核细胞减少症，改变循环单核细胞的表型，增加肺中单核细胞衍生的巨噬细胞，并限制损伤。因此，组织缺氧改变了免疫反应的动力学，从而损害了宿主，并且解决异常反应的干预措施为ARDS提供了新的治疗策略。Mirchandani及其同事表明，组织缺氧改变了循环单核细胞的数量和表型以及它们向肺巨噬细胞的分化，这对肺部炎症的解决具有重要意义。
Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS. Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.
登录
查看更多内容
影响因子：
5.6
作者：
Chen WK;Kuo WW;Hsieh DJ;Chang HN;Pai PY;Lin KH;Pan LF;Ho TJ;Viswanadha VP;Huang CY
通讯作者：
Huang CY
影响因子：
4.6
作者：
Lasseaux, Corentin;Fourmaux, Marie-Pierre;Poulin, Lionel Franz
通讯作者：
Poulin, Lionel Franz
影响因子：
24.3
作者：
Laan, M;Prause, O;Lindén, A
通讯作者：
Lindén, A
影响因子：
15.9
作者：
Bedoret, Denis;Wallemacq, Hugues;Bureau, Fabrice
通讯作者：
Bureau, Fabrice
影响因子：
20.3
作者：
de Bruin, Alexander M.;Libregts, Sten F.;Nolte, Martijn A.
通讯作者：
Nolte, Martijn A.