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Elimination of Granulocytic Myeloid‐Derived Suppressor Cells in Lupus‐Prone Mice Linked to Reactive Oxygen Species–Dependent Extracellular Trap Formation
Author(s) -
Vlachou Katerina,
Mintzas Konstantinos,
Glymenaki Maria,
Ioannou Marianna,
Papadaki Garyfalia,
Bertsias George K.,
Sidiropoulos Prodromos,
Boumpas Dimitrios T.,
Verginis Panayotis
Publication year - 2016
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39441
Subject(s) - systemic lupus erythematosus , immunology , flow cytometry , immune system , myeloid derived suppressor cell , reactive oxygen species , cell sorting , cytokine , biology , chemistry , microbiology and biotechnology , suppressor , disease , medicine , pathology , gene , biochemistry
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.