Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Oct 1;183(7):4693-704.
doi: 10.4049/jimmunol.0802626. Epub 2009 Sep 4.

CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis

Oliver M Steinmetz  1 , Jan-Eric Turner, Hans-Joachim Paust, Matthias Lindner, Anett Peters, Kirstin Heiss, Joachim Velden, Helmut Hopfer, Susanne Fehr, Thorsten Krieger, Catherine Meyer-Schwesinger, Tobias N Meyer, Udo Helmchen, Hans-Willi Mittrücker, Rolf A K Stahl, Ulf Panzer
Affiliations

CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis

Oliver M Steinmetz et al. J Immunol. .

Abstract

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-Fas(lpr) (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-gamma-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-gamma- 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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources