Chemokine Receptor Ccr2 Deficiency Reduces Renal Disease and Prolongs Survival in MRL/lpr Lupus-Prone Mice
| Autor: | Tobias J. Franz, Holger Maier, Guillermo Pérez de Lema, Holger Schmid, Klaus Pfeffer, Bernhard Banas, Dirk H. Busch, Natalia Camarasa, Bruno Luckow, Maríia Escribese, Silvia Chilla, Stephan Segerer, Francisco Mampaso, Svetoslav Kalaydjiev, Detlef Schlöndorff |
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| Rok vydání: | 2005 |
| Předmět: |
Mice
Inbred MRL lpr CCR2 animal diseases 610 Medizin Lupus nephritis Enzyme-Linked Immunosorbent Assay urologic and male genital diseases medicine.disease_cause Sensitivity and Specificity Autoimmunity Mice Immune system Risk Factors immune system diseases parasitic diseases medicine Animals Lupus Erythematosus Systemic skin and connective tissue diseases Autoimmune disease Lupus erythematosus Systemic lupus erythematosus Reverse Transcriptase Polymerase Chain Reaction business.industry Biopsy Needle General Medicine medicine.disease Immunohistochemistry Lupus Nephritis Survival Rate Disease Models Animal Fluorescent Antibody Technique Direct Nephrology Immunology Disease Progression Receptors Chemokine business CD8 |
| Zdroj: | Journal of the American Society of Nephrology. 16:3592-3601 |
| ISSN: | 1046-6673 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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