CXCR3 Mediates Renal Th1 and Th17 Immune Response in Murine Lupus Nephritis
| Autor: | Tobias N. Meyer, Udo Helmchen, Thorsten Krieger, Ulf Panzer, Oliver M. Steinmetz, Rolf A.K. Stahl, Matthias Lindner, Hans-Joachim Paust, Hans-Willi Mittrücker, Susanne Fehr, Jan-Eric Turner, Anett Peters, Kirstin Heiss, Helmut Hopfer, Joachim Velden, Catherine Meyer-Schwesinger |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Mice Inbred MRL lpr Receptors CXCR3 T cell Immunology Lupus nephritis chemical and pharmacologic phenomena Biology Kidney urologic and male genital diseases CXCR3 Mice Immune system Cell Movement immune system diseases medicine Animals Humans Lupus Erythematosus Systemic Immunology and Allergy skin and connective tissue diseases Mice Knockout Lupus erythematosus Interleukin-17 Kidney metabolism hemic and immune systems Th1 Cells medicine.disease Lupus Nephritis Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Immunoglobulin G Female Nephritis |
| Zdroj: | The Journal of Immunology. 183:4693-4704 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0802626 |
| Popis: | Infiltration of T cells into the kidney is a typical feature of human and experimental lupus nephritis that contributes to renal tissue injury. The chemokine receptor CXCR3 is highly expressed on Th1 cells and is supposed to be crucial for their trafficking into inflamed tissues. In this study, we explored the functional role of CXCR3 using the MRL/MpJ-Faslpr (MRL/lpr) mouse model of systemic lupus erythematosus that closely resembles the human disease. CXCR3−/− mice were generated and backcrossed into the MRL/lpr background. Analysis of 20-wk-old CXCR3−/− MRL/lpr mice showed amelioration of nephritis with reduced glomerular tissue damage and decreased albuminuria and T cell recruitment. Most importantly, not only the numbers of renal IFN-γ-producing Th1 cells, but also of IL-17-producing Th17 cells were significantly reduced. Unlike in inflamed kidneys, there was no reduction in the numbers of IFN-γ- or IL-17-producing T cells in spleens, lymph nodes, or the small intestine of MRL/lpr CXCR3−/− mice. This observation suggests impaired trafficking of effector T cells to injured target organs, rather than the inability of CXCR3−/− mice to mount efficient Th1 and Th17 immune responses. These findings show a crucial role for CXCR3 in the development of experimental lupus nephritis by directing pathogenic effector T cells into the kidney. For the first time, we demonstrate a beneficial effect of CXCR3 deficiency through attenuation of both the Th1 and the newly defined Th17 immune response. Our data therefore identify the chemokine receptor CXCR3 as a promising therapeutic target in lupus nephritis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|