Immune Netw.  2020 Apr;20(2):e18. 10.4110/in.2020.20.e18.

Expansion of Myeloid-Derived Suppressor Cells Correlates with Renal Progression in Type 2 Diabetic Nephropathy

Affiliations
  • 1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
  • 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea
  • 3Kidney Research Institute, Seoul National University Hospital, Seoul 03080, Korea
  • 4Wide River Institute of Immunology, Seoul National University College of Medicine, Hongcheon 25159, Korea
  • 5Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Korea
  • 6Research Institute, ProGen Inc., Seongnam 13488, Korea

Abstract

Type 2 diabetic nephropathy (T2DN) progresses with an increasingly inflammatory milieu, wherein various immune cells are relevant. Herein, we investigated the levels of myeloid-derived suppressor cells (MDSCs) and their clinical implication in patients with T2DN. A total of 91 subjects (T2DN, n=80; healthy, n=11) were recruited and their PBMCs were used for flow cytometric analysis of polymorphonuclear (PMN-) and monocytic (M-) MDSCs, in addition to other immune cell subsets. The risk of renal progression was evaluated according to the quartiles of MDSC levels using the Cox model. The proportion of MDSCs in T2DN patients was higher than in healthy individuals (median, 6.7% vs. 2.5%). PMN-MDSCs accounted for 96% of MDSCs, and 78% of PMN-MDSCs expressed Lox-1. The expansion of PMN-MDSCs was not related to the stage of T2DN or other kidney disease parameters such as glomerular filtration rate and proteinuria. The production of ROS in PMN-MDSCs of patients was higher than in neutrophils of patients or in immune cells of healthy individuals, and this production was augmented under hyperglycemic conditions. The 4th quartile group of PMN-MDSCs had a higher risk of renal progression than the 1st quartile group, irrespective of adjusting for multiple clinical and laboratory variables. In conclusion, PMN-MDSCs are expanded in patients with T2DN, and may represent as an immunological biomarker of renal progression.

Keyword

Diabetic nephropathy; End-stage renal disease; Immunology; Monocyte; Myeloid-derived suppressor cell
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