Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney.
Reperfusion following ischemia is associated with acute kidney injury and inflammation. Using a mouse model, we exposed the kidney to a nonlethal period of ischemia, rendering it refractory to future ischemia-induced dysfunction. This ischemic preconditioning is partially mediated by Treg lymphocytes that suppress immune responses. We found that this maneuver significantly inhibited the accumulation of neutrophils and macrophages, tubular necrosis, and loss of kidney function caused by a subsequent ischemia/reperfusion injury 1 week later. The initial ischemia/reperfusion caused a significant increase in CD4(+)CD25(+)FoxP3(+) and CD4(+)CD25(+)IL-10(+) Treg cells within the kidney at 7 days of reperfusion. Treatment of preconditioned mice with a Treg cell-depleting antibody (PC61) reversed the effect of preconditioning on kidney neutrophil accumulation and partially inhibited the functional and histological protection of preconditioning. Adoptive transfer of Treg cells in naive mice, before ischemia/reperfusion, mimicked the protective and anti-inflammatory effects of ischemic preconditioning on the kidney. These studies highlight the role of Treg cells in ischemic preconditioning.
Kinsey
Gilbert R
GR
Division of Nephrology and Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Huang
Liping
L
Vergis
Amy L
AL
Li
Li
L
Okusa
Mark D
MD
D058186:Acute Kidney Injury / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D019264:Adoptive Transfer; D000818:Animals; D007249:Inflammation / Q000150:complications / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007511:Ischemia / Q000150:complications / Q000276:immunology / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D016753:Interleukin-10