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Article: CXCL9, but not CXCL10, promotes CXCR3-dependent immune-mediated kidney disease

TitleCXCL9, but not CXCL10, promotes CXCR3-dependent immune-mediated kidney disease
Authors
Issue Date2008
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal of the American Society of Nephrology, 2008, v. 19 n. 6, p. 1177-1189 How to Cite?
AbstractChemokines are instrumental in macrophage- and T cell-dependent diseases. The chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis (MRL.-Faslpr mice and the nephrotoxic serum nephritis model), but evidence suggests that multiple chemokines are involved. For identification of additional therapeutic targets for immune-mediated nephritis, chemokine ligands and receptors in CCL2-/- and wild-type (WT) MRL-Faslpr kidneys were profiled. The focus was on intrarenal chemokine ligand/receptor pairs that were highly upregulated downstream of CCL2; the chemokine CXCL10 and its cognate receptor, CXCR3, stood out as potential therapeutic targets. However, renal disease was not suppressed in CXCL10 -/- MRL-Faslpr mice, and CXCLKT-/- C57BL/6 mice were not protected from nephrotoxic serum nephritis compared with WT mice. Because CXCR3 engages with the ligand CXCL9, CXCR3 -/- , CXCL9 -/-, and CXCLICT-/- B6 mice were compared with WT mice with nephrotoxic serum nephritis. Kidney disease, measured by loss of renal function and histopathology, was suppressed in both CXCR3-/- and CXCL9-/- mice but not in CXCLKT-/- mice. With nephrotoxic serum nephritis, CXCR3-/- and CXCL9-/- mice had fewer intrarenal activated T cells and activated macrophages. Both IgG glomerular deposits and antigen-specific IgG in serum were reduced in these mice, suggesting that although CXCR3 and CXCL9 initiate nephritis through cell-mediated events, renal inflammation may be sustained by their regulation of IgG. It is concluded that specific blockade of CXCL9 or CXCR3 may be a potential therapeutic target for human immune-mediated kidney diseases. Copyright © 2008 by the American Society of Nephrology.
Persistent Identifierhttp://hdl.handle.net/10722/225924
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorMenke, J-
dc.contributor.authorZeller, GC-
dc.contributor.authorKikawada, E-
dc.contributor.authorMeans, TK-
dc.contributor.authorHuang, XR-
dc.contributor.authorLan, HY-
dc.contributor.authorLu, B-
dc.contributor.authorFarber, J-
dc.contributor.authorLuster, AD-
dc.contributor.authorKelley, VR-
dc.date.accessioned2016-05-25T03:23:32Z-
dc.date.available2016-05-25T03:23:32Z-
dc.date.issued2008-
dc.identifier.citationJournal of the American Society of Nephrology, 2008, v. 19 n. 6, p. 1177-1189-
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/225924-
dc.description.abstractChemokines are instrumental in macrophage- and T cell-dependent diseases. The chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis (MRL.-Faslpr mice and the nephrotoxic serum nephritis model), but evidence suggests that multiple chemokines are involved. For identification of additional therapeutic targets for immune-mediated nephritis, chemokine ligands and receptors in CCL2-/- and wild-type (WT) MRL-Faslpr kidneys were profiled. The focus was on intrarenal chemokine ligand/receptor pairs that were highly upregulated downstream of CCL2; the chemokine CXCL10 and its cognate receptor, CXCR3, stood out as potential therapeutic targets. However, renal disease was not suppressed in CXCL10 -/- MRL-Faslpr mice, and CXCLKT-/- C57BL/6 mice were not protected from nephrotoxic serum nephritis compared with WT mice. Because CXCR3 engages with the ligand CXCL9, CXCR3 -/- , CXCL9 -/-, and CXCLICT-/- B6 mice were compared with WT mice with nephrotoxic serum nephritis. Kidney disease, measured by loss of renal function and histopathology, was suppressed in both CXCR3-/- and CXCL9-/- mice but not in CXCLKT-/- mice. With nephrotoxic serum nephritis, CXCR3-/- and CXCL9-/- mice had fewer intrarenal activated T cells and activated macrophages. Both IgG glomerular deposits and antigen-specific IgG in serum were reduced in these mice, suggesting that although CXCR3 and CXCL9 initiate nephritis through cell-mediated events, renal inflammation may be sustained by their regulation of IgG. It is concluded that specific blockade of CXCL9 or CXCR3 may be a potential therapeutic target for human immune-mediated kidney diseases. Copyright © 2008 by the American Society of Nephrology.-
dc.languageeng-
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org-
dc.relation.ispartofJournal of the American Society of Nephrology-
dc.subject.meshChemokine CXCL10 - physiology-
dc.subject.meshChemokine CXCL9 - physiology-
dc.subject.meshMice-
dc.subject.meshNephritis - etiology - immunology-
dc.subject.meshReceptors, CXCR3 - physiology-
dc.titleCXCL9, but not CXCL10, promotes CXCR3-dependent immune-mediated kidney disease-
dc.typeArticle-
dc.identifier.emailHuang, XR: xlan@hkucc.hku.hk-
dc.identifier.emailLan, HY: hylan@hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1681/ASN.2007111179-
dc.identifier.pmid18337479-
dc.identifier.pmcidPMC2396941-
dc.identifier.hkuros146502-
dc.identifier.volume19-
dc.identifier.issue6-
dc.identifier.spage1177-
dc.identifier.epage1189-
dc.publisher.placeUnited States-

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