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 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.
Author: | Jianghong Zhong, Tatjana Scholz, Anthony C. Y. Yau, Simon Guerard, Ulrike Hüffmeier, Harald BurkhardtORCiDGND, Rikard Holmdahl |
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URN: | urn:nbn:de:hebis:30:3-465449 |
DOI: | https://doi.org/10.1126/sciadv.aas9864 |
ISSN: | 2375-2548 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/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 |
Page Number: | 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 / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (English): | Creative Commons - Namensnennung-Nicht kommerziell 4.0 |