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RESEARCH ARTICLE
IKKα is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells
Xin Wan, Li-Jun Hou, Li-Yuan Zhang, Wen-Juan Huang, Lin Liu, Qian Zhang, Bo Hu, Wen Chen, Xin Chen, Chang-Chun Cao
Disease Models & Mechanisms 2015 8: 733-742; doi: 10.1242/dmm.018200
Xin Wan
Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Li-Jun Hou
Division of Neurosurgery, Department of Surgery and Shanghai Neurosurgical Institute, The Second Military Medical University, Changzheng Hospital, Shanghai 200003, China
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Li-Yuan Zhang
Division of Nephrology, Department of Medicine, Affiliated Lianyungang Clinical Medical College of Nanjing Medical University, Lianyungang 222002, China
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Wen-Juan Huang
Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Lin Liu
Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Qian Zhang
Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Bo Hu
Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Wen Chen
Division of Cardiovascular Surgery, Department of Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Xin Chen
Division of Cardiovascular Surgery, Department of Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Chang-Chun Cao
Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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  • For correspondence: caochangchun@njmu.edu.cn
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ABSTRACT

The recovery phase after kidney ischemia/reperfusion (IR) injury is often associated with the suppression of inflammation and the proliferation of tubular epithelial cells (TECs). The duration of this phase is often determined by the suppression of inflammation and the proliferation of TECs. Several lines of evidence suggest that IκB kinase α (IKKα) not only promotes the production of anti-inflammatory factors and/or prevents the production of inflammatory factors, but also induces the accompanying cell differentiation and regeneration, and suppresses inflammation. We therefore hypothesized that IKKα could participate in the kidney repair after IR injury and have used a mouse model of acute kidney injury (AKI) to test this. We found that IKKα mediated the repair of the kidney via infiltrated regulatory T (Treg) cells, which can produce anti-inflammatory cytokine IL10, and that IKKα also increased the proliferation of the surviving TECs and suppressed of inflammation. In addition, the expression of indoleamine 2,3-dioxygenase (IDO) in TECs is consistent with the infiltration of IL10-producing Treg cells. We conclude that IKKα is involved in kidney recovery and regeneration through the Treg cells that can produce IL10, which might be a potential therapeutic target that can be used to promote kidney repair after IR injury.

Footnotes

  • ↵* These authors contributed equally to this work

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    X.W. and L.-J.H. contributed equally to this work. All authors read and approved the final manuscript.

  • Funding

    This work was supported by grants from the National Natural Science Foundation of China [81170658 and 81370797].

  • Supplementary material

    Supplementary material available online at http://dmm.biologists.org/lookup/suppl/doi:10.1242/dmm.018200/-/DC1

  • Received September 10, 2014.
  • Accepted April 17, 2015.
  • © 2015. Published by The Company of Biologists Ltd

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Keywords

  • IκB kinase α
  • Kidney
  • Ischemia-reperfusion injury
  • Repair
  • IL10
  • T regular cell
  • Indoleamine 2
  • 3-dioxygenase

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RESEARCH ARTICLE
IKKα is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells
Xin Wan, Li-Jun Hou, Li-Yuan Zhang, Wen-Juan Huang, Lin Liu, Qian Zhang, Bo Hu, Wen Chen, Xin Chen, Chang-Chun Cao
Disease Models & Mechanisms 2015 8: 733-742; doi: 10.1242/dmm.018200
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RESEARCH ARTICLE
IKKα is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells
Xin Wan, Li-Jun Hou, Li-Yuan Zhang, Wen-Juan Huang, Lin Liu, Qian Zhang, Bo Hu, Wen Chen, Xin Chen, Chang-Chun Cao
Disease Models & Mechanisms 2015 8: 733-742; doi: 10.1242/dmm.018200

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