Renal dendritic cells ameliorate nephrotoxic acute kidney injury.
Inflammation contributes to the pathogenesis of acute kidney injury. Dendritic cells (DCs) are immune sentinels with the ability to induce immunity or tolerance, but whether they mediate acute kidney injury is unknown. Here, we studied the distribution of DCs within the kidney and the role of DCs in cisplatin-induced acute kidney injury using a mouse model in which DCs express both green fluorescence protein and the diphtheria toxin receptor. DCs were present throughout the tubulointerstitium but not in glomeruli. We used diphtheria toxin to deplete DCs to study their functional significance in cisplatin nephrotoxicity. Mice depleted of DCs before or coincident with cisplatin treatment but not at later stages experienced more severe renal dysfunction, tubular injury, neutrophil infiltration and greater mortality than nondepleted mice. We used bone marrow chimeric mice to confirm that the depletion of CD11c-expressing hematopoietic cells was responsible for the enhanced renal injury. Finally, mixed bone marrow chimeras demonstrated that the worsening of cisplatin nephrotoxicity in DC-depleted mice was not a result of the dying or dead DCs themselves. After cisplatin treatment, expression of MHC class II decreased and expression of inducible co-stimulator ligand increased on renal DCs. These data demonstrate that resident DCs reduce cisplatin nephrotoxicity and its associated inflammation.
Tadagavadi
Raghu K
RK
Department of Biochemistry and Molecular Biology, Penn State University College of Medicine, Hershey, Pennsylvania, PA, USA.
Reeves
W Brian
WB
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D039521:CD11c Antigen / Q000378:metabolism; D002945:Cisplatin; D003713:Dendritic Cells / Q000473:pathology* / Q000502:physiology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009399:Nephrons / Q000473:pathology / Q000503:physiopathology
D039521:CD11c Antigen; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D049452:Green Fluorescent Proteins; D002945:Cisplatin