Regulation of inflammation by the antioxidant haem oxygenase 1

• Published in: Nature reviews. Immunology Vol. 21; no. 7; pp. 411 - 425
• Main Authors: Campbell, Nicole K., Fitzgerald, Hannah K., Dunne, Aisling
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2021; Nature Publishing Group
• Subjects: 631/250/256; 631/443/319; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - immunology; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants; Antioxidants - metabolism; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; Carbon monoxide; Carbon Monoxide - metabolism; Care and treatment; Dendritic Cells - immunology; Dendritic Cells - metabolism; Development and progression; Enzyme Induction - drug effects; Gene Expression Regulation, Enzymologic; Health aspects; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - immunology; Heme Oxygenase-1 - metabolism; Humans; Immunology; Immunomodulation; Inflammation; Inflammation - drug therapy; Inflammation - enzymology; Inflammation - immunology; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - immunology; Iron; Macrophages - immunology; Macrophages - metabolism; Medical treatment; Metabolism; Models, Biological; Multiple Sclerosis - drug therapy; Multiple Sclerosis - enzymology; Multiple Sclerosis - immunology; Oxidoreductases; Oxygenase; Physiological aspects; Phytochemicals - therapeutic use; Pneumonia - drug therapy; Pneumonia - enzymology; Pneumonia - immunology; Psoriasis - drug therapy; Psoriasis - enzymology; Psoriasis - immunology; Review Article; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transplantation Immunology; Ireland
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/s41577-020-00491-x

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. This Review provides an overview of haem oxygenase 1 (HO-1) for immunologists, including its roles in iron metabolism and antioxidant defence, and the impact of HO-1 induction in specific immune cell populations. The authors highlight the therapeutic potential of HO-1 induction for treatment of chronic inflammatory and autoimmune diseases.