The role of Tregs and CD11c(+) macrophages/dendritic cells in ischemic preconditioning of the kidney

Kidney Int. 2010 Nov;78(10):981-92. doi: 10.1038/ki.2010.266. Epub 2010 Aug 4.

Abstract

Dendritic cells have the potential to induce tolerance and here we attempted to identify their role in the tolerance seen in ischemic pre-conditioning. We induced bilateral renal ischemic preconditioning in mice and then challenged them with an ischemic insult 7 days later. Compared to sham-operated controls, preconditioned mice were found to have reduced injury with less inflammation, but had an increased number of regulatory T cells (Tregs) in their kidneys after the delayed insult. Splenocytes from these mice had more Tregs and mature CD11c(+) cells, but reduced proliferative and cytokine-secretory responses, suggesting a state of immunosuppression compared to control mice. Anti-CD25 depletion followed by adoptive transfer of Tregs partially mitigated and then restored the protective effect of preconditioning. Depletion of CD11c(+) cells with liposomes containing clodronate was associated with partial loss of preconditioning benefits. The increased numbers of Tregs or impaired immune response found in splenocytes from preconditioned mice were partially reversed in splenocytes from liposome clodronate-treated animals, suggesting that CD11c(+) cells contribute to immune cell-mediated ischemic preconditioning. Hence, our results show that ischemic preconditioning of the kidney provides a negative signal to the peripheral immune system, partially mediating the tissue-protective and anti-inflammatory effects of this maneuver.

MeSH terms

  • Animals
  • CD11c Antigen / metabolism*
  • CD4 Antigens / metabolism
  • Cell Proliferation
  • Clodronic Acid / administration & dosage
  • Dendritic Cells / physiology*
  • Forkhead Transcription Factors / metabolism
  • Immune System / physiology
  • Immunosuppression
  • Ischemic Preconditioning*
  • Kidney / blood supply*
  • Kidney / metabolism
  • Kidney / pathology
  • Liposomes
  • Macrophages / immunology*
  • Macrophages / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Regional Blood Flow / physiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control
  • Spleen / cytology
  • Spleen / drug effects
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • CD11c Antigen
  • CD4 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Liposomes
  • Clodronic Acid