Mannan-induced Nos2 in macrophages enhances IL-17–driven psoriatic arthritis by innate lymphocytes

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 o
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.
show moreshow less

Metadaten
Author:Jianghong Zhong, Tatjana Scholz, Anthony C. Y. Yau, Simon Guerard, Ulrike Hüffmeier, Harald Burkhardt, Rikard Holmdahl
URN:urn:nbn:de:hebis:30:3-465449
DOI:http://dx.doi.org/10.1126/sciadv.aas9864
ISSN:2375-2548
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29774240
Parent Title (English):Science advances
Publisher:Assoc.
Place of publication:Washington, DC [u. a.]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/05/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/06/12
Volume:4
Issue:5, eaas9864
Pagenumber:11
First Page:1
Last Page:10
Note:
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
HeBIS PPN:434444847
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0

$Rev: 11761 $