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IL-2/anti-IL-2 complex attenuates renal ischemia-reperfusion injury through expansion of regulatory T cells

Academic Article
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Overview

authors

  • Kim, M. G.
  • Koo, T. Y.
  • Yan, J. J.
  • Lee, E.
  • Han, K. H.
  • Jeong, J. C.
  • Ro, H.
  • Kim, B. S.
  • Jo, S. K.
  • Oh, K. H.
  • Surh, Charles
  • Ahn, C.
  • Yang, J.

publication date

  • October 2013

journal

  • Journal of the American Society of Nephrology  Journal

abstract

  • Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemia-reperfusion injury (IRI), but the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate renal IRI in mice. IL-2C administered before bilateral renal IRI induced Treg expansion in both spleen and kidney, improved renal function, and attenuated histologic renal injury and apoptosis after IRI. Furthermore, IL-2C administration reduced the expression of inflammatory cytokines and attenuated the infiltration of neutrophils and macrophages in renal tissue. Depletion of Tregs with anti-CD25 antibodies abrogated the beneficial effects of IL-2C. However, IL-2C-mediated renal protection was not dependent on either IL-10 or TGF-β. Notably, IL-2C administered after IRI also enhanced Treg expansion in spleen and kidney, increased tubular cell proliferation, improved renal function, and reduced renal fibrosis. In conclusion, these results indicate that IL-2C-induced Treg expansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Cell Differentiation
  • Drug Evaluation, Preclinical
  • Fibrosis
  • Interleukin-2
  • Kidney
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Renal Insufficiency
  • Reperfusion Injury
  • T-Lymphocytes, Regulatory
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Identity

PubMed Central ID

  • PMC3785269

International Standard Serial Number (ISSN)

  • 1046-6673

Digital Object Identifier (DOI)

  • 10.1681/ASN.2012080784

PubMed ID

  • 23833258
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Additional Document Info

start page

  • 1529

end page

  • 1536

volume

  • 24

issue

  • 10

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