title: Reactive Oxygen Species Regulate Innate But Not Adaptive Inflammation in ZAP70-Mutated SKG Arthritic Mice.
abstract: Polysaccharides from Saccharomyces cerevisiae can induce arthritis, ileitis, and interstitial pneumonitis in BALB/c ZAP70 (W163C)-mutant (SKG) mice via T helper 17-cell-dependent pathways. However, little is known regarding the factors influencing disease severity. We investigated mannan-induced arthritis in SKG mice and how NADPH oxidase 2-derived reactive oxygen species (ROS) regulate disease. SKG mice were highly susceptible to both IL-17-mediated T-cell-driven arthritis and T-cell-independent acute psoriasis-like dermatitis. In vivo imaging revealed more ROS in joints of arthritic SKG mice compared to wild-type mice, which links ROS and joint inflammation. Still, ROS deficiency in SKG.Ncf1(m1j/m1j) mice greatly increased severity of arthritis and dermatitis, a difference that could not be attributed to increased T-cell activation, thymic selection, or antibody production. However, when ROS production was restored in CD68(+) macrophages, inflammation reverted to baseline, demonstrating a regulatory role of macrophage-derived ROS in autoimmunity. Thus, arthritis in SKG mice is a useful model to study the role of ROS in innate-driven chronic inflammation independently of adaptive immunity.
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Guerard
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Electronic address: kajsa.wing@ki.se.
authors.forename: Kajsa
authors.initials: K
authors.lastname: Wing
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017382:Reactive Oxygen Species / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse