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Updated: Apr 17, 2026
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Germ-free mice deficient of reactive oxygen species have increased arthritis susceptibility
Kajsa Wing1, Katrin Klocke1, Annika Samuelsson2
1Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Abstract:
The NADPH oxidase 2 (NOX2) complex is responsible for the production of ROS in phagocytic cells. Genetic defects in NOX2 lead to opportunistic infections and inflammatory manifestations such as granulomas in humans, also known as chronic granulomatous disease (CGD). This condition is mirrored in mice with defective ROS production and interestingly both species are predisposed to autoimmune diseases. An unresolved question is whether the hyper-inflammation and tendency to develop autoimmunity are secondary to the increased infections, or whether these are parallel phenomena. We generated germ-free ROS deficient Ncf1 mutant mice that when reared in specific pathogen-free condition, are highly susceptible to collagen-induced arthritis compared with wild-type mice. Strikingly, arthritis incidence and severity was almost identical in germ-free and specific pathogen-free ROS-deficient mice. In addition, partial reduction of the microbial flora by antibiotics treatment did not alter the disease course. Taken together, this shows that ROS has a clear immune regulatory function that is decoupled from its function in host defence.
Insights
Reactive oxygen species (ROS) regulate immunity independently of infection defense. ROS-deficient mice show high susceptibility to autoimmune arthritis, regardless of microbial exposure, highlighting ROS immune function.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- The NADPH oxidase 2 (NOX2) complex generates reactive oxygen species (ROS) in phagocytes.
- NOX2 defects cause chronic granulomatous disease (CGD), leading to infections and autoimmunity.
- It remains unclear if autoimmunity in CGD is due to infections or is a parallel phenomenon.
Purpose of the Study:
- To investigate the immune regulatory role of ROS independently of host defense.
- To determine if ROS deficiency predisposes to autoimmune diseases even in the absence of microbial challenges.
Main Methods:
- Generated germ-free ROS-deficient Ncf1 mutant mice.
- Compared susceptibility to collagen-induced arthritis in germ-free vs. specific pathogen-free (SPF) ROS-deficient mice.
- Assessed the impact of antibiotic treatment on disease severity in ROS-deficient mice.
Main Results:
- ROS-deficient mice, whether germ-free or SPF, exhibited high susceptibility to collagen-induced arthritis.
- Arthritis incidence and severity were comparable between germ-free and SPF ROS-deficient mice.
- Antibiotic treatment did not alter the autoimmune disease course in ROS-deficient mice.
Conclusions:
- ROS possess a distinct immune regulatory function separate from their role in combating infections.
- The predisposition to autoimmune diseases in ROS deficiency is decoupled from increased susceptibility to opportunistic infections.
