Immune Modulation by Myeloid-Derived Suppressor Cells in Diabetic Kidney Disease

• Published in: International journal of molecular sciences 2022-11, Vol.23 (21), p.13263
• Main Authors: Hsieh, Ching-Chuan, Chang, Cheng-Chih, Hsu, Yung-Chien, Lin, Chun-Liang
• Format: Article
• Language: English
• Subjects: Anti-inflammatory agents; Apoptosis; Arginine; Autophagy; Body weight; Cell cycle; Cell proliferation; Colony-stimulating factor; Depletion; Diabetes; Diabetes mellitus; diabetic kidney disease; Diabetic nephropathy; End-stage renal disease; Endothelial cells; Extracellular matrix; Fibronectin; Fibrosis; Glucose; Granulocyte-macrophage colony stimulating factor; Immunomodulation; Immunoregulation; Immunotherapy; Inflammation; Interleukin 6; Kidney diseases; Kinases; Lymphocytes; Lymphocytes T; Mesangial cells; myeloid-derived suppressor cell; Oxidative stress; Phosphorylation; Proteins; Review; Suppressor cells; Therapeutic targets; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232113263

Diabetic kidney disease (DKD) frequently leads to end-stage renal disease and other life-threatening illnesses. The dysregulation of glomerular cell types, including mesangial cells, endothelial cells, and podocytes, appears to play a vital role in the development of DKD. Myeloid-derived suppressor cells (MDSCs) exhibit immunoregulatory and anti-inflammatory properties through the depletion of L-arginine that is required by T cells, through generation of oxidative stress, interference with T-cell recruitment and viability, proliferation of regulatory T cells, and through the promotion of pro-tumorigenic functions. Under hyperglycemic conditions, mouse mesangial cells reportedly produce higher levels of fibronectin and pro-inflammatory cytokines. Moreover, the number of MDSCs is noticeably decreased, weakening inhibitory immune activities, and creating an inflammatory environment. In diabetic mice, immunotherapy with MDSCs that were induced by a combination of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1β, and IL-6, reduced kidney to body weight ratio, fibronectin expression, and fibronectin accumulation in renal glomeruli, thus ameliorating DKD. In conclusion, MDSCs exhibit anti-inflammatory activities that help improve renal fibrosis in diabetic mice. The therapeutic targeting of the proliferative or immunomodulatory pathways of MDSCs may represent an alternative immunotherapeutic strategy for DKD.