1. Expansion of Polymorphonuclear Myeloid-Derived Suppressor Cells in Patients With Gout
- Author
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Limei Zhong, Sitao Li, Yi Wen, Junhui Zheng, Fengbin Liu, Donglin Cao, and Yufeng Liu
- Subjects
Male ,0301 basic medicine ,Neutrophils ,T-Lymphocytes ,Cell Culture Techniques ,Lymphocyte Activation ,Pathogenesis ,Mice ,chemistry.chemical_compound ,immunosuppressive ,0302 clinical medicine ,Immunology and Allergy ,Medicine ,Cells, Cultured ,Original Research ,T cell function ,medicine.diagnostic_test ,Middle Aged ,medicine.anatomical_structure ,Disease Progression ,Cytokines ,Female ,Inflammation Mediators ,medicine.symptom ,Adult ,lcsh:Immunologic diseases. Allergy ,musculoskeletal diseases ,T cell ,Immunology ,monosodium urate crystals ,Inflammation ,Immunophenotyping ,Flow cytometry ,03 medical and health sciences ,gout ,In vivo ,Animals ,Humans ,business.industry ,Myeloid-Derived Suppressor Cells ,medicine.disease ,Coculture Techniques ,Gout ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Case-Control Studies ,Myeloid-derived Suppressor Cell ,Polymorphonuclear myeloid-derived suppressor cell ,Uric acid ,Reactive Oxygen Species ,lcsh:RC581-607 ,business ,Biomarkers ,030215 immunology - Abstract
Gout is an inflammatory joint disease caused by monosodium urate (MSU) crystals; however, the mechanism underlying MSU-induced inflammation is unclear. Previous research has suggested that inflammation or cancer can drive the expansion of myeloid-derived suppressor cells (MDSCs). In this study, the role of MDSCs in MSU-induced gout inflammation was evaluated. A total of 28 patients with gout, and 20 healthy controls were recruited for the study. MDSCs, and their functions, were analyzed by flow cytometry and a T cell co-culture assay, respectively. We observed a higher frequency of PMN-MDSCs, and a stronger immunosuppressive function, in patients with gout compared to the controls. Moreover, circulating PMN-MDSCs were positively correlated with pathological indicators, including uric acid and C-reactive protein levels. We also demonstrated that MSU can induce significant PMN-MDSC expansion, using in vivo and in vitro experiments. Finally, MSU-induced PMN-MDSCs produced higher levels of IL-1β, which mediated gout inflammatory progression. Our results demonstrate that MSU modulates the expansion and suppressive function of PMN-MDSCs, providing insights into a novel mechanism underlying the pathogenesis of MSU-induced gout. Thus, MDSCs may be useful for the development of novel therapeutic strategies for the prevention and treatment of gout.
- Published
- 2020