Glucocorticoid-Induced Leucine Zipper Promotes Neutrophil and T Cell Polarization with Protective Effects in Acute Kidney Injury

摘要: The glucocorticoid-induced leucine zipper (GILZ) mediates anti-inflammatory effects of glucocorticoids. Acute kidney injury (AKI) mobilizes immune/inflammatory mechanisms, causing tissue injury, but GILZ9s impact in AKI is not known. Neutrophils play context-specific pro- (N1) and (N2) functional roles. Also, regulatory T lymphocytes (Tregs) T-17 (Treg17) cells exert counter-inflammatory including suppression effector lymphocytes, e.g., Th-17 cells. Thus, utilizing cell preparations mice kidneys subjected to or sham operation, we determined the GILZ on neutrophil subtypes context its renoprotective effect; these studies utilized trans activator transcription (TAT)-GILZ TAT peptide. increased N1 reduced N2, Tregs Treg17 association with interleukin (IL)-17+ IL-10+ accompanied disruption mitochondrial membrane potential (ψm) apoptosis/necrosis compared kidneys. TAT-GILZ, TAT, treatment N2 Tregs, without affecting cells, reduction IL-17+ cells; TAT-GILZ caused less ψm death AKI. Importantly, perfusion ischemic-reperfused edema TAT. Utilizing splenic bone marrow-derived neutrophils, further showed marked proliferation Th response than Collectively, results indicate that exerts renoprotection upregulation regulatory/suppressive arm immunity likely via regulating crosstalk between neutrophils.