| First Author | Guerard S | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 9 | Pages | 2353-63 |
| PubMed ID | 27427418 | Mgi Jnum | J:235142 |
| Mgi Id | MGI:5792983 | Doi | 10.1016/j.ajpath.2016.05.014 |
| Citation | Guerard S, et al. (2016) Reactive Oxygen Species Regulate Innate But Not Adaptive Inflammation in ZAP70-Mutated SKG Arthritic Mice. Am J Pathol 186(9):2353-63 |
| abstractText | 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. |
