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If it's not one thing, HIF's another: immunoregulation by hypoxia inducible factors in disease.
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-07-06 , DOI: 10.1111/febs.15476 Ffion R Hammond 1 , Amy Lewis 1 , Philip M Elks 1
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-07-06 , DOI: 10.1111/febs.15476 Ffion R Hammond 1 , Amy Lewis 1 , Philip M Elks 1
Affiliation
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Hypoxia‐inducible factors (HIFs) have emerged in recent years as critical regulators of immunity. Localised, low oxygen tension is a hallmark of inflamed and infected tissues. Subsequent myeloid cell HIF stabilisation plays key roles in the innate immune response, alongside emerging oxygen‐independent roles. Manipulation of regulatory proteins of the HIF transcription factor family can profoundly influence inflammatory profiles, innate immune cell function and pathogen clearance and, as such, has been proposed as a therapeutic strategy against inflammatory diseases. The direction and mode of HIF manipulation as a therapy are dictated by the inflammatory properties of the disease in question, with innate immune cell HIF reduction being, in general, advantageous during chronic inflammatory conditions, while upregulation of HIF is beneficial during infections. The therapeutic potential of targeting myeloid HIFs, both genetically and pharmacologically, has been recently illuminated in vitro and in vivo, with an emerging range of inhibitory and activating strategies becoming available. This review focuses on cutting edge findings that uncover the roles of myeloid cell HIF signalling on immunoregulation in the contexts of inflammation and infection and explores future directions of potential therapeutic strategies.
中文翻译：
如果不是一回事，HIF 就是另一回事：疾病中缺氧诱导因子的免疫调节。
近年来，缺氧诱导因子 (HIF) 已成为免疫的关键调节因子。局部低氧张力是发炎和感染组织的标志。随后的骨髓细胞 HIF 稳定在先天免疫反应中起关键作用，同时出现了不依赖氧的作用。操纵 HIF 转录因子家族的调节蛋白可以深刻影响炎症特征、先天免疫细胞功能和病原体清除，因此，已被提议作为针对炎症性疾病的治疗策略。HIF 操作作为一种疗法的方向和模式取决于所讨论疾病的炎症特性，先天免疫细胞 HIF 减少通常在慢性炎症条件下是有利的，而 HIF 的上调在感染期间是有益的。最近阐明了在基因和药理学上靶向骨髓 HIF 的治疗潜力在体外和体内，一系列新兴的抑制和激活策略变得可用。本综述侧重于揭示骨髓细胞 HIF 信号传导在炎症和感染情况下对免疫调节的作用的前沿发现，并探索潜在治疗策略的未来方向。
更新日期：2020-07-06
中文翻译：
如果不是一回事，HIF 就是另一回事：疾病中缺氧诱导因子的免疫调节。
近年来，缺氧诱导因子 (HIF) 已成为免疫的关键调节因子。局部低氧张力是发炎和感染组织的标志。随后的骨髓细胞 HIF 稳定在先天免疫反应中起关键作用，同时出现了不依赖氧的作用。操纵 HIF 转录因子家族的调节蛋白可以深刻影响炎症特征、先天免疫细胞功能和病原体清除，因此，已被提议作为针对炎症性疾病的治疗策略。HIF 操作作为一种疗法的方向和模式取决于所讨论疾病的炎症特性，先天免疫细胞 HIF 减少通常在慢性炎症条件下是有利的，而 HIF 的上调在感染期间是有益的。最近阐明了在基因和药理学上靶向骨髓 HIF 的治疗潜力在体外和体内，一系列新兴的抑制和激活策略变得可用。本综述侧重于揭示骨髓细胞 HIF 信号传导在炎症和感染情况下对免疫调节的作用的前沿发现，并探索潜在治疗策略的未来方向。
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