title: Chronicity following ischaemia-reperfusion injury depends on tubular-macrophage crosstalk involving two tubular cell-derived CSF-1R activators: CSF-1 and IL-34.
abstract: Two structurally unrelated ligands activate the macrophage colony stimulating factor receptor (CSF-1R, c-fms, CD115): M-CSF/CSF-1 and interleukin-34 (IL-34). Both ligands promote macrophage proliferation, survival and differentiation. IL-34 also activates the protein-tyrosine phosphatase ζ receptor (PTP-ζ, PTPRZ1). Both receptors and cytokines are increased during acute kidney injury. While tubular cell-derived CSF-1 is required for kidney repair, Baek et al (J Clin Invest 2015; 125: 3198-3214) have now identified tubular epithelial cell-derived IL-34 as a promoter of kidney neutrophil and macrophage infiltration and tubular cell destruction during experimental kidney ischaemia-reperfusion, leading to chronic injury. IL-34 promoted proliferation of both intrarenal macrophages and bone marrow cells, increasing circulating neutrophils and monocytes and their kidney recruitment. Thus, injured tubular cells release two CSF-1R activators, one (CSF-1) that promotes tubular cell survival and kidney repair and another (IL-34) that promotes chronic kidney damage. These results hold promise for the development of IL-34-targeting strategies to prevent ischaemia-reperfusion kidney injury in contexts such as kidney transplantation. However, careful consideration should be given to the recent characterization by Bezie et al. (J Clin Invest 2015; 125: 3952-3964) of IL-34 as a T regulatory cell (Treg) cytokine that modulates macrophage responses so that IL-34-primed macrophages potentiate the immune suppressive capacity of Tregs and promote graft tolerance.
authors.affiliation: IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain REDINREN, Madrid, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.affiliation: IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain REDINREN, Madrid, Spain.
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Sanz
authors.affiliation: IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain REDINREN, Madrid, Spain School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain Fundacion Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: inflammation; kidney; macrophages; tolerance; transplantation