Regulation of inflammation by the antioxidant haem oxygenase 1

Nat Rev Immunol. 2021 Jul;21(7):411-425. doi: 10.1038/s41577-020-00491-x. Epub 2021 Jan 29.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / immunology
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / metabolism*
  • Carbon Monoxide / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Enzyme Induction / drug effects
  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / immunology
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / enzymology*
  • Inflammation / immunology
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / enzymology
  • Inflammatory Bowel Diseases / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Models, Biological
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / enzymology
  • Multiple Sclerosis / immunology
  • Phytochemicals / therapeutic use
  • Pneumonia / drug therapy
  • Pneumonia / enzymology
  • Pneumonia / immunology
  • Psoriasis / drug therapy
  • Psoriasis / enzymology
  • Psoriasis / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transplantation Immunology

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Phytochemicals
  • Carbon Monoxide
  • Heme Oxygenase-1