Reactive Oxygen Species Regulate Innate But Not Adaptive Inflammation in ZAP70-Mutated SKG Arthritic Mice.
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| 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.
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| Authors | Simon Guerard, Rikard Holmdahl, Kajsa Wing |
| Journal | The American journal of pathology (Am J Pathol) Vol. 186 Issue 9 Pg. 2353-63 (09 2016) ISSN: 1525-2191 [Electronic] United States |
| PMID | 27427418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
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