CXCL9, but not CXCL10, Promotes CXCR3-Dependent Immune-Mediated Kidney Disease
In: Journal of the American Society of Nephrology, Jg. 19 (2008), Heft 6, S. 1177-1189
Online
academicJournal
- print, 54 ref
Zugriff:
Chemokines are instrumental in macrophage- and T cell-dependent diseases. The chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis (MRL-FasIpr 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-FasIpr 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-FasIpr mice, and CXCL10-/- C57BL/6 mice were not protected from nephrotoxic serum nephritis compared with WT mice. Because CXCR3 engages with the ligand CXCL9, CXCR3-/-, CXCL9-/-, and CXCL10-/- 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 CXCL10-/- 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.
Titel: |
CXCL9, but not CXCL10, Promotes CXCR3-Dependent Immune-Mediated Kidney Disease
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Autor/in / Beteiligte Person: | MENKE, Julia ; ZELLER, Geraldine C ; KIKAWADA, Eriya ; MEANS, Terry K ; HUANG, Xiao R ; LAN, Han Y ; BAO, LU ; FARBER, Joshua ; LUSTER, Andrew D ; KELLEY, Vicki R |
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Zeitschrift: | Journal of the American Society of Nephrology, Jg. 19 (2008), Heft 6, S. 1177-1189 |
Veröffentlichung: | Hagerstown, MD: Lippincott Williams & Wilkins, 2008 |
Medientyp: | academicJournal |
Umfang: | print, 54 ref |
ISSN: | 1046-6673 (print) |
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