IL-4/IL-13-mediated polarization of renal macrophages/dendritic cells to an M2a phenotype is essential for recovery from acute kidney injury.

Zhang MZ, Wang X, Wang Y, Niu A, Wang S, Zou C, Harris RC
Kidney Int. 2017 91 (2): 375-386

PMID: 27745702 · PMCID: PMC5548101 · DOI:10.1016/j.kint.2016.08.020

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.

Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

MeSH Terms (24)

Acute Kidney Injury Animals Cell Plasticity Dendritic Cells Diphtheria Toxin Disease Models, Animal Fibrosis Genotype Heparin-binding EGF-like Growth Factor Interleukin-4 Interleukin-13 Janus Kinase 3 Kidney Macrophages Male Mice, 129 Strain Mice, Inbred BALB C Mice, Knockout Phenotype Recovery of Function Reperfusion Injury Signal Transduction STAT6 Transcription Factor Time Factors

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