Reactive Oxygen Species Dynamics in Autoimmune Pathologies

Reactive oxygen species (ROS) are chemically reactive molecules derived primarily from molecular oxygen, generated by specialised enzymes within phagocytes and other cell types. In autoimmune disease, a finely tuned balance of ROS production and removal governs both host defence and tissue integrity. Excessive or misplaced ROS can drive aberrant inflammation, leading to oxidative damage of lipids, proteins and DNA, whereas insufficient ROS impairs immune regulation and antigen clearance. Recent advances reveal that ROS modulate key signalling pathways in neutrophils, macrophages and lymphocytes, influencing cytokine release, cell death programmes and antigen presentation. Dysregulation of ROS contributes to the pathogenesis of systemic lupus erythematosus, rheumatoid arthritis and other chronic autoimmune disorders by altering T-cell activation, B-cell receptor signalling and macrophage polarisation. A deeper understanding of ROS dynamics is informing novel therapeutic strategies—ranging from targeted antioxidants to controlled flux of oxidative bursts—with the potential to restore immune homeostasis without compromising pathogen defence.

Research from Nature Portfolio

Investigations have shown that neutrophil-derived ROS drive the transition of inflammatory monocytes into reparative macrophages, orchestrating the resolution of tissue inflammation. In models of sterile injury, depletion of ROS-producing neutrophils impaired macrophage phenotypic conversion and delayed repair, while reconstitution with ROS-competent cells restored homeostasis. Complementary work has elucidated an intracellular signalling axis in which NADPH oxidase activity controls thioredoxin-1 redox state to limit NF-κB-driven hyperinflammation. Genetic or pharmacological loss of NOX2 led to reductive stress in immune cells, exaggerated cytokine responses and heightened disease severity, suggesting that calibrated ROS generation is essential to prevent autoimmune-like hyperactivation.

Reactive Oxygen Species Dynamics in Autoimmune Pathologies publication trend

The graph below shows the total number of articles in reactive oxygen species dynamics in autoimmune pathologies across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Partially reduced oxygen derivatives, such as superoxide and hydrogen peroxide, acting as both signalling mediators and antimicrobial effectors.

NADPH oxidase (NOX2): A multi-subunit enzyme complex in phagocytes that transfers electrons from NADPH to oxygen, generating ROS during the oxidative burst.

Oxidative burst: Rapid release of ROS by activated phagocytes, essential for microbial killing and initiation of redox-sensitive signalling cascades.

Neutrophil extracellular traps (NETs): Web-like structures composed of chromatin and antimicrobial proteins, released by neutrophils in a ROS-dependent manner to trap pathogens.

Macrophage polarisation: The spectrum of macrophage activation states, from pro-inflammatory (M1) to pro-resolving (M2), influenced by redox cues.

Toll-like receptor 7 (TLR7): An endosomal pattern-recognition receptor sensing RNA ligands; its activity is modulated by local ROS to calibrate autoantigen responses.

References

1. Phosphopeptides P140 cause oxidative burst responses of pulmonary macrophages in an imiquimod-induced lupus model. Molecular Biomedicine (2023).
2. NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7. JCI Insight (2024).
3. Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair. Nature Communications (2019).
4. Apocynin and Nox2 regulate NF-κB by modifying thioredoxin-1 redox-state. Scientific Reports (2016).
5. A Role for NADPH Oxidase in Antigen Presentation. Frontiers in Immunology (2013).
6. A New Arthritis Therapy with Oxidative Burst Inducers. PLOS Medicine (2006).