2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006111237v1 18/7/2071    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Panzer, U. Articles by Stahl, R. A.K. Search for Related Content PubMed PubMed Citation Articles by Panzer, U. Articles by Stahl, R. A.K.

Chemokine Receptor CXCR3 Mediates T Cell Recruitment and Tissue Injury in Nephrotoxic Nephritis in Mice

Ulf Panzer^*, Oliver M. Steinmetz^*, Hans-Joachim Paust^*, Catherine Meyer-Schwesinger^*, Anett Peters^*, Jan-Eric Turner^*, Gunther Zahner^*, Felix Heymann, Christian Kurts, Helmut Hopfer, Udo Helmchen, Friedrich Haag, André Schneider^* and Rolf A.K. Stahl^*

^* Medizinische Klinik III, Institut für Pathologie, and Institut für Immunologie, Universitätsklinikum Hamburg Eppendorf, Hamburg, and Institute for Molecular Medicine and Experimental Immunology, Universitätsklinikum Bonn, Bonn, Germany

Correspondence: Dr. Rolf A.K. Stahl, Medizinische Klinik III, Zentrum für Innere Medizin, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. Phone: +49-40-42803-4020; Fax: +49-40-42803-5186; E-mail: rstahl{at}uke.uni-hamburg.de

Received for publication November 13, 2006. Accepted for publication April 4, 2007.

The chemokine receptor CXCR3 is highly expressed on Th1 polarized T cells and has been predicted to play an important role in T cell recruitment and immune response in a number of inflammatory and autoimmune diseases. For testing whether CXCR3 plays a role in renal inflammation, CXCR3-deficient mice were generated and nephrotoxic nephritis was induced in C57BL/6 CXCR3^–/– and C57BL/6 wild-type mice. Induction of the nephrotoxic nephritis leads to an increased renal mRNA expression of IP-10/CXCL10 (8.6-fold), Mig/CXCL9 (2.3-fold), and I-TAC/CXCL11 (4.9-fold) during the autologous phase at days 7 and 14. This increased chemokine expression was paralleled by the renal infiltration of T cells, followed by renal tissue injury, albuminuria, and loss of renal function. Compared with wild-type mice, CXCR3-deficient mice had significantly reduced renal T cell infiltrates. Moreover, CXCR3^–/– mice developed less severe nephritis, with significantly lower albuminuria, better renal function, and a reduced frequency of glomerular crescent formation. Nephritic wild-type and CXCR3^–/– mice both elicited an efficient systemic nephritogenic immune response in terms of antigen-specific IgG production and IFN- expression by splenocytes in response to the nephritogenic antigen. These findings indicate that the ameliorated nephritis in CXCR3-deficient mice is due to impaired renal trafficking of effector T cells rather than their inability to mount an efficient humoral or cellular immune response. The neutralization of CXCR3 might be a promising therapeutic strategy for Th1-dependent inflammatory renal disease.

This article has been cited by other articles:

				J.-E. Turner, H.-J. Paust, O. M. Steinmetz, A. Peters, C. Meyer-Schwesinger, F. Heymann, U. Helmchen, S. Fehr, R. Horuk, U. Wenzel, et al. CCR5 Deficiency Aggravates Crescentic Glomerulonephritis in Mice J. Immunol., November 1, 2008; 181(9): 6546 - 6556. [Abstract] [Full Text] [PDF]

				J. Menke, G. C. Zeller, E. Kikawada, T. K. Means, X. R. Huang, H. Y. Lan, B. Lu, J. Farber, A. D. Luster, and V. R. Kelley CXCL9, but not CXCL10, Promotes CXCR3-Dependent Immune-Mediated Kidney Disease J. Am. Soc. Nephrol., June 1, 2008; 19(6): 1177 - 1189. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673