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Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2018 Mar; Vol. 29 (3), pp. 961-976. Date of Electronic Publication: 2018 Jan 02. - Publication Year :
- 2018
-
Abstract
- 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.<br /> (Copyright © 2018 by the American Society of Nephrology.)
- Subjects :
- Amphiregulin metabolism
Animals
Female
Humans
Immunity, Innate
Interleukin-13 metabolism
Interleukin-4 metabolism
Kidney Diseases immunology
Kidney Diseases pathology
Lymphocyte Count
Macrophages immunology
Male
Mice
Recombinant Proteins therapeutic use
Reperfusion Injury immunology
Reperfusion Injury pathology
T-Lymphocytes, Regulatory immunology
Th2 Cells immunology
Interleukin-33 therapeutic use
Kidney Diseases prevention & control
Lymphocytes immunology
Lymphocytes metabolism
Reperfusion Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 29295873
- Full Text :
- https://doi.org/10.1681/ASN.2017070774