Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye.
Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye.
复制标题
低氧诱导因素对于髓样细胞迁移到发炎的小鼠眼中是可剂量的。
DOI：
10.1038/srep40830
复制
发表时间：
2017-01-23
影响因子：
4.6
通讯作者：
Bainbridge JW
中科院分区：
文献类型：
--
作者：
Gardner PJ;Liyanage SE;Cristante E;Sampson RD;Dick AD;Ali RR;Bainbridge JW
缺氧诱导因子（Hypoxia inducible factors, hif）是一种在动态氧水平下对细胞稳态起重要作用的转录因子。髓细胞特异性hfs对髓细胞功能的各个方面至关重要，包括它们在自身免疫性疾病期间迁移到炎症组织的能力。这与骨髓细胞在缺血和缺氧部位的积累是由于缺乏趋化反应的概念形成对比。在这里，我们试图解决hif在人类葡萄膜炎小鼠模型炎症期间髓细胞运输中的作用。我们用骨髓特异性cre缺失hfs的小鼠表明，骨髓性hfs对于白细胞迁移到发炎的眼睛是必不可少的。髓细胞特异性缺失Hif1a、Epas1，或两者同时缺失，对迁移到眼睛的髓细胞数量没有影响。此外，通过删除髓细胞中的Vhl来稳定HIF通路对髓细胞向发炎眼睛的运输没有影响。最后，我们通过溶血性贫血化学诱导低氧血症，从而在循环白细胞中稳定HIF，以证明HIF在骨髓细胞向发炎眼睛迁移中不可或缺的作用。这些数据表明，与之前的报道相反，炎症和缺氧期间髓细胞中的HIF通路对于髓细胞组织运输是必不可少的。
Hypoxia inducible factors (HIFs) are ubiquitously expressed transcription factors important for cell homeostasis during dynamic oxygen levels. Myeloid specific HIFs are crucial for aspects of myeloid cell function, including their ability to migrate into inflamed tissues during autoimmune disease. This contrasts with the concept that accumulation of myeloid cells at ischemic and hypoxic sites results from a lack of chemotactic responsiveness. Here we seek to address the role of HIFs in myeloid trafficking during inflammation in a mouse model of human uveitis. We show using mice with myeloid-specific Cre-deletion of HIFs that myeloid HIFs are dispensable for leukocyte migration into the inflamed eye. Myeloid-specific deletion of Hif1a, Epas1, or both together, had no impact on the number of myeloid cells migrating into the eye. Additionally, stabilization of HIF pathways via deletion of Vhl in myeloid cells had no impact on myeloid trafficking into the inflamed eye. Finally, we chemically induce hypoxemia via hemolytic anemia resulting in HIF stabilization within circulating leukocytes to demonstrate the dispensable role of HIFs in myeloid cell migration into the inflamed eye. These data suggest, contrary to previous reports, that HIF pathways in myeloid cells during inflammation and hypoxia are dispensable for myeloid cell tissue trafficking.