Redox regulation of immunometabolism

Nat Rev Immunol. 2021 Jun;21(6):363-381. doi: 10.1038/s41577-020-00478-8. Epub 2020 Dec 18.


Metabolic pathways and redox reactions are at the core of life. In the past decade(s), numerous discoveries have shed light on how metabolic pathways determine the cellular fate and function of lymphoid and myeloid cells, giving rise to an area of research referred to as immunometabolism. Upon activation, however, immune cells not only engage specific metabolic pathways but also rearrange their oxidation-reduction (redox) system, which in turn supports metabolic reprogramming. In fact, studies addressing the redox metabolism of immune cells are an emerging field in immunology. Here, we summarize recent insights revealing the role of reactive oxygen species (ROS) and the differential requirement of the main cellular antioxidant pathways, including the components of the thioredoxin (TRX) and glutathione (GSH) pathways, as well as their transcriptional regulator NF-E2-related factor 2 (NRF2), for proliferation, survival and function of T cells, B cells and macrophages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Glutathione / immunology
  • Glutathione / metabolism
  • Humans
  • Lymphocyte Activation
  • Macrophages / immunology
  • Macrophages / metabolism
  • Metabolic Networks and Pathways / immunology*
  • Models, Biological
  • Models, Immunological
  • NF-E2-Related Factor 2 / immunology
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Thioredoxins / immunology
  • Thioredoxins / metabolism


  • Antioxidants
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Thioredoxins
  • Glutathione