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
- Authors
- Kim, Myung-Gyu; Cho, Eun Jung; Lee, Jae Won; Ko, Yoon Sook; Lee, Hee Young; Jo, Sang-Kyung; Cho, Won Yong; Kim, Hyoung Kyu
- Issue Date
- 1월-2014
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- acute kidney injury; heat-shock protein-70; immunomodulation; regulatory T cells
- Citation
- KIDNEY INTERNATIONAL, v.85, no.1, pp.62 - 71
- Indexed
- SCIE
SCOPUS
- Journal Title
- KIDNEY INTERNATIONAL
- Volume
- 85
- Number
- 1
- Start Page
- 62
- End Page
- 71
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/99710
- DOI
- 10.1038/ki.2013.277
- ISSN
- 0085-2538
- 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.
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