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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. 29:961-976
- Publication Year :
- 2018
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 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.
- Subjects :
- Male
0301 basic medicine
Adoptive cell transfer
Inflammation
urologic and male genital diseases
Amphiregulin
T-Lymphocytes, Regulatory
Mice
03 medical and health sciences
Th2 Cells
0302 clinical medicine
medicine
Animals
Humans
Lymphocyte Count
Lymphocytes
cardiovascular diseases
Tissue homeostasis
Kidney
Interleukin-13
Innate immune system
urogenital system
business.industry
Macrophages
Innate lymphoid cell
General Medicine
Interleukin-33
Immunity, Innate
Recombinant Proteins
Interleukin 33
Basic Research
030104 developmental biology
medicine.anatomical_structure
Nephrology
Reperfusion Injury
030220 oncology & carcinogenesis
Immunology
Humanized mouse
Female
Kidney Diseases
Interleukin-4
medicine.symptom
business
Subjects
Details
- ISSN :
- 15333450 and 10466673
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....434311d6ce5b7725f351a3f61936b392