Mannan-induced Nos2 in macrophages enhances IL-17-driven psoriatic arthritis by innate lymphocytes
Zhong J, Scholz T, Yau ACY, Guerard S, Hüffmeier U, Burkhardt H, Holmdahl R (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 4
Journal Issue: 5
Abstract
Previous identification of the inducible nitric oxide synthase (NOS2) gene as a risk allele for psoriasis (Ps) and psoriatic arthritis (PsA) suggests a possible pathogenic role of nitric oxide (NO). Using a mouse model of mannan-induced Ps and PsA (MIP), where macrophages play a regulatory role by releasing reactive oxygen species (ROS), we found that NO was detectable before disease onset in mice, independent of a functional nicotinamide adenine dinucleotide phosphate oxidase 2 complex. MIP was suppressed by either deletion of Nos2 or inhibition of NO synthases with NG-nitro-l-arginine methyl ester, demonstrating that Nos2-derived NO is pathogenic. NOS2 expression was also up-regulated in lipopolysaccharide- and interferon-γ-stimulated monocyte subsets from patients with PsA compared to healthy controls. Nos2-dependent interleukin-1α (IL-1α) release from skin macrophages was essential for arthritis development by promoting IL-17 production of innate lymphoid cells. We conclude that Nos2-derived NO by tissue macrophages promotes MIP, in contrast to the protective effect by ROS.
Authors with CRIS profile
Involved external institutions
Sweden (SE)
Germany (DE)How to cite
APA:
Zhong, J., Scholz, T., Yau, A.C.Y., Guerard, S., Hüffmeier, U., Burkhardt, H., & Holmdahl, R. (2018). Mannan-induced Nos2 in macrophages enhances IL-17-driven psoriatic arthritis by innate lymphocytes. Science Advances, 4(5). https://doi.org/10.1126/sciadv.aas9864
MLA:
Zhong, Jianghong, et al. "Mannan-induced Nos2 in macrophages enhances IL-17-driven psoriatic arthritis by innate lymphocytes." Science Advances 4.5 (2018).
BibTeX: Download