2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text (Rapid PDF) Supplemental Data All Versions of this Article: ASN.2009040407v1 ASN.2009040407v2 21/1/53    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tadagavadi, R. K. Articles by Reeves, W. B. PubMed PubMed Citation Articles by Tadagavadi, R. K. Articles by Reeves, W. B.

Renal Dendritic Cells Ameliorate Nephrotoxic Acute Kidney Injury

Raghu K. Tadagavadi^* and W. Brian Reeves

^* Department of Biochemistry and Molecular Biology and
Division of Nephrology, Penn State University College of Medicine, Hershey, Pennsylvania; and
Lebanon VA Medical Center, Lebanon, Pennsylvania

Correspondence: Dr. W. Brian Reeves, Division of Nephrology, Room C5830, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033. Phone: 717-531-8156; Fax: 717-531-6776; E-mail: wreeves{at}psu.edu

Received for publication April 16, 2009. Accepted for publication September 13, 2009.

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.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673