| First Author | Zhong J | Year | 2018 |
| Journal | Sci Adv | Volume | 4 |
| Issue | 5 | Pages | eaas9864 |
| PubMed ID | 29774240 | Mgi Jnum | J:288132 |
| Mgi Id | MGI:6415761 | Doi | 10.1126/sciadv.aas9864 |
| Citation | Zhong J, et al. (2018) Mannan-induced Nos2 in macrophages enhances IL-17-driven psoriatic arthritis by innate lymphocytes. Sci Adv 4(5):eaas9864 |
| abstractText | 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-gamma-stimulated monocyte subsets from patients with PsA compared to healthy controls. Nos2-dependent interleukin-1alpha (IL-1alpha) 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. |
