School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Nat Rev Immunol. 2021 Jul;21(7):411-425. doi: 10.1038/s41577-020-00491-x. Epub 2021 Jan 29.
Haem oxygenase 1 (HO-1), an inducible enzyme responsible for the breakdown of haem, is primarily considered an antioxidant, and has long been overlooked by immunologists. However, research over the past two decades in particular has demonstrated that HO-1 also exhibits numerous anti-inflammatory properties. These emerging immunomodulatory functions have made HO-1 an appealing target for treatment of diseases characterized by high levels of chronic inflammation. In this Review, we present an introduction to HO-1 for immunologists, including an overview of its roles in iron metabolism and antioxidant defence, and the factors which regulate its expression. We discuss the impact of HO-1 induction in specific immune cell populations and provide new insights into the immunomodulation that accompanies haem catabolism, including its relationship to immunometabolism. Furthermore, we highlight the therapeutic potential of HO-1 induction to treat chronic inflammatory and autoimmune diseases, and the issues faced when trying to translate such therapies to the clinic. Finally, we examine a number of alternative, safer strategies that are under investigation to harness the therapeutic potential of HO-1, including the use of phytochemicals, novel HO-1 inducers and carbon monoxide-based therapies.
血红素加氧酶 1(HO-1)是一种诱导型酶,负责分解血红素,主要被认为是一种抗氧化剂,长期以来一直被免疫学家忽视。然而,特别是在过去二十年的研究表明,HO-1 还具有许多抗炎特性。这些新出现的免疫调节功能使 HO-1 成为治疗以慢性炎症水平升高为特征的疾病的有吸引力的靶标。在这篇综述中,我们为免疫学家介绍了 HO-1,包括其在铁代谢和抗氧化防御中的作用,以及调节其表达的因素。我们讨论了 HO-1 在特定免疫细胞群中的诱导作用,并提供了关于伴随血红素分解代谢的免疫调节的新见解,包括其与免疫代谢的关系。此外,我们强调了 HO-1 诱导治疗慢性炎症和自身免疫性疾病的治疗潜力,以及在将此类治疗转化为临床实践时面临的问题。最后,我们研究了一些正在研究中的替代、更安全的策略,以利用 HO-1 的治疗潜力,包括使用植物化学物质、新型 HO-1 诱导剂和基于一氧化碳的治疗方法。