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

Won Yong Cho, Hye Min Choi, So Young Lee, Myung Gyu Kim, Hyoung Kyu Kim, Sang Kyung Jo

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)981-992
Number of pages12
JournalKidney International
Volume78
Issue number10
DOIs
Publication statusPublished - 2010 Nov

Keywords

  • dendritic cell
  • immune cell
  • ischemic preconditioning
  • liposome clodronate
  • regulatory T cell

ASJC Scopus subject areas

  • Nephrology

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