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Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury.

  • Cao, Qi1, 2, 3
  • Wang, Yiping4
  • Niu, Zhiguo2, 3
  • Wang, Chengshi4
  • Wang, Ruifeng4
  • Zhang, Zhiqiang4
  • Chen, Titi4
  • Wang, Xin Maggie5
  • Li, Qing4
  • Lee, Vincent W S4
  • Huang, Qingsong2, 3
  • Tan, Jing6
  • Guo, Minghao6
  • Wang, Yuan Min7
  • Zheng, Guoping4
  • Yu, Di8
  • Alexander, Stephen I7
  • Wang, Hui9, 3
  • Harris, David C H1
  • 1 Centre for Transplant and Renal Research and [email protected] [email protected]
  • 2 Henan Key Laboratory of Immunology and Targeted Therapy, and.
  • 3 Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, China. , (China)
  • 4 Centre for Transplant and Renal Research and.
  • 5 Flow Cytometry Facility, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia. , (Australia)
  • 6 Department of Nephrology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. , (China)
  • 7 Centre for Kidney Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia; and. , (Australia)
  • 8 Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, Australia. , (Australia)
  • 9 Henan Key Laboratory of Immunology and Targeted Therapy, and [email protected] [email protected]
Published Article
Journal of the American Society of Nephrology
American Society of Nephrology
Publication Date
Mar 01, 2018
DOI: 10.1681/ASN.2017070774
PMID: 29295873


The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33-treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo-expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo-expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33-ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy. Copyright © 2018 by the American Society of Nephrology.

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