Bignon, Alexandre, Gaudin, Françoise, Hémon, Patrice, Tharinger, Hugo, Loetscher, Pius, Peuchmaur, Michel, Berrebi, Dominique and Balabanian, Karl (2013) Pivotal role of Ccr1 in murine lupus nephritis. Journal of Immunology.

Abstract

Systemic Lupus Erythematosus is a chronic, inflammatory autoimmune disease that affects multiple organs including the kidney. Mononuclear cell infiltration in both glomerular and tubulointerstitial compartments characterizes human and experimental lupus nephritis and is associated with a progressive loss of renal function. Molecular recruitment mechanisms into chronically inflamed kidneys have not been fully characterized especially in the lupus-prone New Zealand Black/New Zealand White (NZB/W) mouse model. By combining pharmacologic and functional approaches, we uncover a previously unappreciated role for the chemokine receptor Ccr1 in renal infiltration of myeloid and T cells in nephritis NZB/W mice. We revealed a functional expression of Ccr1 on peripheral T cells, macrophages and neutrophils from NZB/W mice. Acute treatment of nephritis NZB/W mice with the orally available Ccr1 antagonist BL5923 reduced kidney recruitment of myeloid and T cells, while sparing B cells. Late onset BL5923-based treatment delayed proteinuria and death in nephritis mice. This is likely related to the beneficial effect of Ccr1 blockade on interstitial infiltration of T cells and macrophages as well as on tubulointerstitial and glomerular injuries. In contrast, systemic and renal humoral autoimmunity was unaffected in BL5923-treated mice. Altogether, these findings highlight a pivotal role for Ccr1 in recruiting T and myeloid cells to inflamed kidneys of NZB/W mice and that such activity contributes to the progression of renal injury.

Item Type:	Article
Keywords:	chemokine, chemokine receptor antagonist CCR1 antagonist lupus nephritis
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/9139