Chemokine receptor Ccr2 deficiency reduces renal disease and prolongs survival in MRL/lpr lupus-prone mice.

J Am Soc Nephrol 2005 Dec 2;16(12):3592-601. Epub 2005 Nov 2.

Klinikum der Universität München, Medizinische Poliklinik - Innenstadt, Munich, Germany.

MRL/MpJ-Fas(lpr)/J (MRL/lpr) mice represent a well-established mouse model of human systemic lupus erythematosus. MRL/lpr mice homozygous for the spontaneous lymphoproliferation mutation (lpr) are characterized by systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, splenomegaly, hypergammaglobulinemia, arthritis, and fatal immune complex-mediated glomerulonephritis. It was reported previously that steady-state mRNA levels for the chemokine (C-C motif) receptor 2 (Ccr2) continuously increase in kidneys of MRL/lpr mice. For examining the role of Ccr2 for development and progression of immune complex-mediated glomerulonephritis, Ccr2-deficient mice were generated and backcrossed onto the MRL/lpr genetic background. Ccr2-deficient MRL/lpr mice developed less lymphadenopathy, had less proteinuria, had reduced lesion scores, and had less infiltration by T cells and macrophages in the glomerular and tubulointerstitial compartment. Ccr2-deficient MRL/lpr mice survived significantly longer than MRL/lpr wild-type mice despite similar levels of circulating immunoglobulins and comparable immune complex depositions in the glomeruli of both groups. Anti-dsDNA antibody levels, however, were reduced in the absence of Ccr2. The frequency of CD8+ T cells in peripheral blood was significantly lower in Ccr2-deficient MRL/lpr mice. Thus Ccr2 deficiency influenced not only monocyte/macrophage and T cell infiltration in the kidney but also the systemic T cell response in MRL/lpr mice. These data suggest an important role for Ccr2 both in the general development of autoimmunity and in the renal involvement of the lupus-like disease. These results identify Ccr2 as an additional possible target for the treatment of lupus nephritis.

Download full-text PDF

Source
http://jasn.asnjournals.org/content/16/12/3592.full.pdf
Web Search
http://www.jasn.org/cgi/doi/10.1681/ASN.2005040426
Publisher Site
http://dx.doi.org/10.1681/ASN.2005040426DOI Listing
December 2005
13 Reads

Publication Analysis

Top Keywords

mrl/lpr mice
28
ccr2-deficient mrl/lpr
12
mrl/lpr
10
mice
10
role ccr2
8
immune complex-mediated
8
ccr2 deficiency
8
receptor ccr2
8
complex-mediated glomerulonephritis
8
ccr2
7
ccr2-deficient
4
glomerulonephritis ccr2-deficient
4
progression immune
4
influenced monocyte/macrophage
4
ccr2 development
4
development progression
4
backcrossed mrl/lpr
4
genetic background
4
background ccr2-deficient
4
mice ccr2
4

Altmetric Statistics

References

(Supplied by CrossRef)

J Am Soc Nephrol 2001

J Am Soc Nephrol 2000

Rheumatology (Oxford) 2004

Similar Publications