title: Germ-free mice deficient of reactive oxygen species have increased arthritis susceptibility.
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.
authors.affiliation: Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Kajsa
authors.initials: K
authors.lastname: Wing
authors.affiliation: Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Katrin
authors.initials: K
authors.lastname: Klocke
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Samuelsson
authors.affiliation: Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D024043:Collagen Type II / Q000276:immunology; D005260:Female; D005856:Germ-Free Life; D006105:Granulomatous Disease, Chronic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D024043:Collagen Type II; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: Animal models; Chronic granulomatous disease; Host defence; NOX2 ROS; Rheumatoid arthritis