Reactive Oxygen Species in Autoimmune Cells: Function, Differentiation, and Metabolism
Open Access
- 25 February 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Accumulated reactive oxygen species (ROS) directly contribute to biomacromolecule damage and influence various inflammatory responses. Reactive oxygen species act as mediator between innate and adaptive immune cells, thereby influencing the antigen-presenting process that results in T cell activation. Evidence from patients with chronic granulomatous disease and mouse models support the function of ROS in preventing abnormal autoimmunity; for example, by supporting maintenance of macrophage efferocytosis and T helper 1/T helper 2 and T helper 17/ regulatory T cell balance. The failure of many anti-oxidation treatments indicates that ROS cannot be considered entirely harmful. Indeed, enhancement of ROS may sometimes be required. In a mouse model of rheumatoid arthritis (RA), absence of NOX2-derived ROS led to higher prevalence and more severe symptoms. In patients with RA, naïve CD4+ T cells exhibit inhibited glycolysis and enhanced pentose phosphate pathway (PPP) activity, leading to ROS exhaustion. In this “reductive” state, CD4+ T cell immune homeostasis is disrupted, triggering joint destruction, together with oxidative stress in the synovium.Keywords
This publication has 162 references indexed in Scilit:
- The Neglected Significance of “Antioxidative Stress”Oxidative Medicine and Cellular Longevity, 2012
- p47phox Directs Murine Macrophage Cell Fate DecisionsThe American Journal of Pathology, 2012
- Structure and Reaction Mechanism in the Heme DioxygenasesBiochemistry, 2011
- Intact indoleamine 2,3-dioxygenase activity in human chronic granulomatous diseaseClinical Immunology, 2010
- Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen speciesProceedings of the National Academy of Sciences of the United States of America, 2010
- NADPH oxidase activity controls phagosomal proteolysis in macrophages through modulation of the lumenal redox environment of phagosomesProceedings of the National Academy of Sciences of the United States of America, 2010
- Deficiency of the DNA repair enzyme ATM in rheumatoid arthritisThe Journal of Experimental Medicine, 2009
- How mitochondria produce reactive oxygen speciesBiochemical Journal, 2008
- Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary PreventionJAMA, 2007
- T cell surface redox levels determine T cell reactivity and arthritis susceptibilityProceedings of the National Academy of Sciences of the United States of America, 2006