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IL-4/IL-13–mediated polarization of renal macrophages/dendritic cells to an M2a phenotype is essential for recovery from acute kidney injury
- Source :
- Kidney International. 91:375-386
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration. Similarly, there was delayed recovery and increased tubulointerstitial fibrosis in these diphtheria toxin-treated mice following tamoxifen-induced deletion of both IL-4 and IL-13, with increased levels of M1 and decreased levels of M2 markers in the macrophages/dendritic cells. Furthermore, deletion of IL-4 and IL-13 led to a decrease of tissue reparative M2a phenotype markers but had no effect on anti-inflammatory M2c phenotype markers. Deletion of IL-4 and IL-13 also inhibited recovery from ischemia-reperfusion injury in association with increased M1 and decreased M2 markers and promoted subsequent tubulointerstitial fibrosis. Thus, IL-4 and IL-13 are required to effectively polarize macrophages/dendritic cells to an M2a phenotype and to promote recovery from acute kidney injury.
- Subjects :
- Male
0301 basic medicine
Mice, 129 Strain
Time Factors
Genotype
Cell Plasticity
Macrophage polarization
Biology
Kidney
Article
03 medical and health sciences
medicine
Renal fibrosis
Animals
Diphtheria Toxin
Interleukin 4
Mice, Knockout
Diphtheria toxin
Mice, Inbred BALB C
Interleukin-13
Macrophages
Acute kidney injury
Janus Kinase 3
Dendritic Cells
Recovery of Function
Acute Kidney Injury
medicine.disease
Fibrosis
Phenotype
Disease Models, Animal
030104 developmental biology
Nephrology
Reperfusion Injury
Interleukin 13
Immunology
Tubulointerstitial fibrosis
Interleukin-4
STAT6 Transcription Factor
Heparin-binding EGF-like Growth Factor
Signal Transduction
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....059762ca52855209f43d89eaaf375abe