The heat-shock protein-70-induced renoprotective effect is partially mediated by CD4+ CD25+ Foxp3+ regulatory T cells in ischemia/reperfusion-induced acute kidney injury

Myung-Gyu Kim, Eun Jung Cho, Jae Won Lee, Yoon Sook Ko, Hee Young Lee, Sang Kyung Jo, Won Yong Cho, Hyoung Kyu Kim

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33 Citations (Scopus)

Abstract

Recent reports suggest the presence of heat-shock protein (HSP)-reactive T cells with a regulatory phenotype in various inflammatory diseases. To test whether HSP exerts renoprotective effects through regulatory T cells (Tregs), ischemia/reperfusion injury was done with or without heat preconditioning in mice. Splenocytes from heat-preconditioned mice had Treg expansion and a reduced proliferative response upon mitogenic stimulus. T cells from heat-preconditioned mice failed to reconstitute postischemic injury when adoptively transferred to T cell-deficient nu/nu mice in contrast to those from control mice. Tregs were also increased in heat-preconditioned ischemic kidneys. Depleting Tregs before heat preconditioning abolished the renoprotective effect, while adoptive transfer of these cells back into Treg-depleted mice partially restored the beneficial effect of heat preconditioning. Inhibition of HSP70 by quercetin suppressed Treg expansion, as well as renoprotective effects. Transferring Tregs in quercetin-treated heat-preconditioned mice partially restored the beneficial effect of heat preconditioning. The specificity of immune cell HSP70 in renoprotection was confirmed by partial restoration of kidney injury when T cells from HSP70-deficient heat preconditioned mice were adoptively transferred to nu/nu mice. Thus, the renoprotective effect of HSP70 may be partially mediated by a direct immunomodulatory effect through Tregs. Better understanding of immunomodulatory mechanisms of various stress proteins might facilitate discovery of new preventive strategies in acute kidney injury

Original languageEnglish
Pages (from-to)62-71
Number of pages10
JournalKidney International
Volume85
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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Keywords

  • acute kidney injury
  • heat-shock protein-70
  • immunomodulation
  • regulatory T cells

ASJC Scopus subject areas

  • Nephrology

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