Back to Search Start Over

Neutrophil-derived mitochondrial DNA promotes receptor activator of nuclear factor κB and its ligand signalling in rheumatoid arthritis.

Authors :
Contis, Anne
Mitrovic, Stéphane
Lavie, Julie
Douchet, Isabelle
Lazaro, Estibaliz
Truchetet, Marie-Elise
Goizet, Cyril
Contin-Bordes, Cécile
Schaeverbeke, Thierry
Blanco, Patrick
Rossignol, Rodrigue
Faustin, Benjamin
Richez, Christophe
Duffau, Pierre
Source :
Rheumatology; Jul2017, Vol. 56 Issue 7, p1200-1205, 6p, 2 Graphs
Publication Year :
2017

Abstract

Objectives. Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils. Methods. The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR. Purified neutrophils were challenged in vitro with Toll-like receptor agonists as well as mtDNA. RANKL expression by neutrophils was studied by flow cytometry. Results. SF neutrophils from RA patients displayed a gene expression signature of oxidative stress. This stress signature was associated with the release of mtDNA in SF as observed by a significant increase of mtDNA in the SF of RA patients compared with OA patients. mtDNA in RA SF was correlated with systemic inflammation as assessed by CRP concentrations. We also showed that mtDNA drives neutrophil RANKL expression to the same extent as Toll-like receptor agonists. Conclusion. Our data identify SF neutrophils as a cellular source of mtDNA that leads to a subsequent expression of RANKL. This highlights the important role of neutrophils in RA osteoimmunology. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14620324
Volume :
56
Issue :
7
Database :
Complementary Index
Journal :
Rheumatology
Publication Type :
Academic Journal
Accession number :
123800031
Full Text :
https://doi.org/10.1093/rheumatology/kex041