title: Expansion of polymorphonuclear myeloid-derived suppressor cells in patients with end-stage renal disease may lead to infectious complications.
abstract: Myeloid-derived suppressor cells (MDSCs) are recently identified immune suppressive cells in multiple chronic inflammations. Here, we investigated MDSCs in patients with end-stage renal disease (ESRD) and their clinical significance in these patients and healthy individuals (49 each). Polymorphonuclear and mononuclear MDSCs were investigated by flow cytometry. Patients with ESRD before hemodialysis presented a significantly higher level of polymorphonuclear MDSCs. Depletion of polymorphonuclear-MDSCs resolved T cell IFN-γ responses. By co-culture, T cell proliferation and the production of IFN-γ were abrogated by the addition of polymorphonuclear MDSCs in a dose-dependent manner. Both of these effects were reversed by a reactive oxygen species inhibitor. The levels of reactive oxygen species were higher in polymorphonuclear MDSCs derived from patients with ESRD than from normal individuals. The mRNA level of NOX2, the key protein complex responsible for reactive oxygen species production, was higher in ESRD-related polymorphonuclear MDSCs. The phospho-STAT3 level, a key activator of MDSCs, was higher in ESRD-related polymorphonuclear MDSCs. Finally, the polymorphonuclear MDSC level before and after hemodialysis was positively related to infectious diseases. Patients with ESRD were dichotomized into 2 groups by the amount of polymorphonuclear MDSCs. Patients with high levels of polymorphonuclear MDSCs presented with a higher incidence of infectious events. Thus, polymorphonuclear MDSCs were elevated in ESRD patients with strong immune-suppressive capability through a phospho-STAT3/reactive oxygen species pathway. Hence, polymorphonuclear MDSCs might increase the risk of infectious complications.
authors.affiliation: Department of Nephrology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; The First Affiliated Hospital of Jinan University, Guangzhou, People's Republic of China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xing
authors.affiliation: Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Cai
authors.affiliation: Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Gynecology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Qing-Jian
authors.initials: QJ
authors.lastname: Ye
authors.affiliation: Department of Orthopedics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ren
authors.affiliation: The First Affiliated Hospital of Jinan University, Guangzhou, People's Republic of China.
authors.forename: Liang-Hong
authors.initials: LH
authors.lastname: Yin
authors.affiliation: Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address: lixing9@mail.sysu.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015994:Incidence; D007239:Infections / Q000453:epidemiology / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000276:immunology* / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D006435:Renal Dialysis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007371:Interferon-gamma; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: end-stage renal disease; myeloid derived suppressor cell; reactive oxygen species