Rapamycin protects kidney against ischemia reperfusion injury through recruitment of NKT cells

BackgroundNKT cells play a protective role in ischemia reperfusion (IR) injury, of which the trafficking in the body and recruitment in injured organs can be influenced by immunosuppressive therapy. Therefore, we investigated the effects of rapamycin on kidneys exposed to IR injury in early stage and on trafficking of NKT cells in a murine model.Material and methodsBalb/c mice were subjected to kidney 30 min ischemia followed by 24 h reperfusion. Rapamycin (2.5 ml/kg) was administered by gavage daily, starting 1 day before the operation. Renal function and histological changes were assessed. The proportion of NKT cells in peripheral blood, spleen and kidney was detected by flow cytometry. The chemokines and corresponding receptor involved in NKT cell trafficking were determined by RT-PCR and flow cytometry respectively.ResultsRapamycin significantly improved renal function and ameliorated histological injury. In rapamycin-treated group, the proportion of NKT cells in spleen was significantly decreased but increased in peripheral blood and kidney. In addition, the CXCR3+ NKT cell in the kidney increased remarkably in the rapamycin-treated group. The chemokines, CXCL9 and CXCL10, as the ligands of CXCR3, were also increased in the rapamycin-treated kidney.ConclusionsRapamycin may recruit NKT cells from spleen to the IR-induced kidney to ameliorate renal IR injury in the early stage.

• Publication year

  2014

• Venue

  Journal of Translational Medicine

• Publication date

  2014-08-19

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/s12967-014-0224-zPMID 25134448PMCID 4145235
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Increased peripheral and local soluble FGL2 in the recovery of renal ischemia reperfusion injury in a porcine kidney auto-transplantation model

  2014cited by this paper
• Helix B surface peptide administered after insult of ischemia reperfusion improved renal function, structure and apoptosis through beta common receptor/erythropoietin receptor and PI3K/Akt pathway in a murine model

  2013cited by this paper
• The effect of mTOR-inhibition on NF-κB activity in kidney ischemia-reperfusion injury in mice.

  2013cited by this paper
• Effects of Everolimus on Oxidative Stress in Kidney Model of Ischemia/Reperfusion Injury

  2013cited by this paper
• Innate immunity activation involved in unprotected porcine auto-transplant kidneys preserved by naked caspase-3 siRNA

  2013cited by this paper
• Sulfatide-reactive natural killer T cells abrogate ischemia-reperfusion injury.

  2011cited by this paper
• Cross‐regulation between distinct natural killer T cell subsets influences immune response to self and foreign antigens

  2009cited by this paper
• Preactivation of NKT cells with alpha-GalCer protects against hepatic ischemia-reperfusion injury in mouse by a mechanism involving IL-13 and adenosine A2A receptor.

  2009cited by this paper
• The multiple facets of mTOR in immunity.

  2009cited by this paper
• NKT Cell Activation Mediates Neutrophil IFN-γ Production and Renal Ischemia-Reperfusion Injury1

  2007cited by this paper
• NKT cell activation mediates neutrophil IFN-gamma production and renal ischemia-reperfusion injury.

  2007influential reference
• The role of immunosuppressive drugs in aggravating renal ischemia and reperfusion injury.

  2007cited by this paper
• The mTOR Inhibitor Everolimus Induces Proteinuria and Renal Deterioration in the Remnant Kidney Model in the Rat

  2007cited by this paper
• Role of NKT cells in allogeneic islet graft survival.

  2007cited by this paper
• The role of heme oxygenase 1 in rapamycin-induced renal dysfunction after ischemia and reperfusion injury.

  2006cited by this paper
• Direct Regulatory Role of NKT Cells in Allogeneic Graft Survival Is Dependent on the Quantitative Strength of Antigenicity1

  2005cited by this paper
• Delayed graft function in kidney transplantation.

  2004cited by this paper
• Differential Chemokine Responses and Homing Patterns of Murine TCRαβ NKT Cell Subsets 1

  2003cited by this paper
• The NKT cell system: bridging innate and acquired immunity

  2003cited by this paper
• Human Immunodeficiency Virus 1 Envelope Glycoprotein Complex-Induced Apoptosis Involves Mammalian Target of Rapamycin/Fkbp12-Rapamycin–Associated Protein–Mediated P53 Phosphorylation

  2001cited by this paper
• Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury.

  1996cited by this paper

• Invariant Natural Killer T Cells in Solid Organ Transplantation

  2026cites this paper
• ANXA1 and ARG2 drive T cell proliferation in ischemia-reperfusion injury: integrated bulk and single-cell transcriptomic analysis

  2025cites this paper
• The role and mechanism of TSC in kidney diseases: a literature review

  2025cites this paper
• NRF1 coordinates mitochondrial adaptations to dampen intracellular ROS and inflammatory responses during ischemia reperfusion

  2025cites this paper
• Twist2 knockdown alleviates renal ischemia–reperfusion injury by maintaining mitochondrial function and enhancing mitophagy through Bnip3

  2025cites this paper
• Podoplanin: A potential therapeutic target for thrombotic diseases

  2023cites this paper
• Rapamycin Alternatively Modifies Mitochondrial Dynamics in Dendritic Cells to Reduce Kidney Ischemic Reperfusion Injury

  2021cites this paper
• Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI Patients

  2021cites this paper
• Unconventional T cells and kidney disease

  2021cites this paper
• CXCR3 alleviates renal ischemia-reperfusion injury via increase of Tregs

  2021cites this paper
• MicroRNA mediated regulation of the major redox homeostasis switch, Nrf2, and its impact on oxidative stress-induced ischemic/reperfusion injury.

  2020cites this paper
• The pathological role of ferroptosis in ischemia/reperfusion-related injury

  2020cites this paper
• Use of Mammalian Target of Rapamycin Inhibitors for Pancreas Transplant Immunosuppression Is Associated With Improved Allograft Survival and Improved Early Patient Survival

  2019cites this paper
• Protective Role of mTOR in Liver Ischemia/Reperfusion Injury: Involvement of Inflammation and Autophagy

  2019cites this paper
• Induction of antiinflammatory purinergic signaling in activated human iNKT cells.

  2018cites this paper
• The Role of Natural Killer T Cells in Acute Kidney Injury: Angel or Evil?

  2017cites this paper
• The mTOR signal regulates myeloid-derived suppressor cells differentiation and immunosuppressive function in acute kidney injury

  2017cites this paper
• NKT cells in cardiovascular diseases.

  2017cites this paper
• Animal Models of Kidney Disease

  2017cites this paper
• Role of mechanistic target of rapamycin (mTOR) in renal function and ischaemia–reperfusion induced kidney injury

  2016cites this paper
• Rapamycin Ameliorates Renal Ischemia/ Reperfusion Injury via Remodeling Immune Microenvironment

  2015cites this paper
• Transcriptional Effects of mTOR Inhibitors on Vascular Smooth Muscle Cells

  2015cites this paper
• T cells in kidney injury and regeneration

  year unknowncites this paper