Elimination of Granulocytic Myeloid-Derived Suppressor Cells in Lupus-Prone Mice Linked to Reactive Oxygen Species-Dependent Extracellular Trap Formation.
Arthritis Rheumatol
; 68(2): 449-61, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26414650
ABSTRACT
OBJECTIVE:
Emerging evidence supports a crucial role of myeloid-derived suppressor cells (MDSCs) in the regulation of autoimmune diseases. However, their role in systemic lupus erythematosus (SLE) remains unknown. This study sought to address the role of MDSCs in the pathogenesis of SLE.METHODS:
MDSCs from (NZB × NZW)F1 lupus-prone mice were assessed for phenotype by flow cytometry, and the function of MDSCs was analyzed by in vitro T cell proliferation assay and real-time quantitative polymerase chain reaction. Extracellular trap (ET) formation was evaluated by immunofluorescence and confocal microscopy. The production of reactive oxygen species (ROS) by Ly-6G+ cells was determined by fluorescence-activated cell sorting analysis.RESULTS:
Expansion of MDSCs was impaired and the function of MDSCs was defective in the lymphoid organs of (NZB × NZW)F1 lupus-prone mice with established disease, in which involvement of predominantly the granulocytic MDSC (G-MDSC) cell subset was observed. More specifically, the results showed that increased elimination of G-MDSCs, driven by the inflammatory milieu of lupus, could be attributed to ET formation, and that cytokines, such as interferon-α (IFNα), IFNγ, and interleukin-6, play a role in this process. Induction of ET release by G-MDSCs was mediated by the production of ROS, since inhibition of ROS generation significantly reduced ET release.CONCLUSION:
Collectively, the results of this study reveal that elimination of a crucial regulatory immune cell subset is a feature of the SLE microenvironment. These findings provide new insights into the pathogenetic mechanisms of the disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Citocinas
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Espécies Reativas de Oxigênio
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Células Precursoras de Granulócitos
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Armadilhas Extracelulares
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Lúpus Eritematoso Sistêmico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arthritis Rheumatol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Grécia