Journal
KIDNEY INTERNATIONAL
Volume 91, Issue 5, Pages 1236-1242Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2016.12.015
Keywords
end-stage renal disease; myeloid derived suppressor cell; reactive oxygen species
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Funding
- National Natural Science Foundation of China [31600710]
- Natural Science Foundation of Guangdong [2014A030313146, 2016A030313302]
- Innovative Training Program of Sun Yat-sen University [201601073]
- Laboratory Open Fund of Sun Yat-sen University [20160117]
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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-gamma responses. By co-culture, T cell proliferation and the production of IFN-gamma 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.
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