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

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CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis. / Steinmetz, Oliver; Turner, Jan Eric; Paust, Hans-Joachim; Lindner, Matthias; Peters, Anett; Heiss, Kirstin; Velden, Joachim; Hopfer, Helmut; Fehr, Susanne; Krieger, Thorsten; Meyer-Schwesinger, Catherine; Meyer, Tobias N; Helmchen, Udo; Mittrücker, Hans Willi; Stahl, Rolf A.K.; Panzer, Ulf.

In: J IMMUNOL, Vol. 183, No. 7, 7, 2009, p. 4693-4704.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Steinmetz, O, Turner, JE, Paust, H-J, Lindner, M, Peters, A, Heiss, K, Velden, J, Hopfer, H, Fehr, S, Krieger, T, Meyer-Schwesinger, C, Meyer, TN, Helmchen, U, Mittrücker, HW, Stahl, RAK & Panzer, U 2009, 'CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis.', J IMMUNOL, vol. 183, no. 7, 7, pp. 4693-4704. <http://www.ncbi.nlm.nih.gov/pubmed/19734217?dopt=Citation>

APA

Steinmetz, O., Turner, J. E., Paust, H-J., Lindner, M., Peters, A., Heiss, K., Velden, J., Hopfer, H., Fehr, S., Krieger, T., Meyer-Schwesinger, C., Meyer, T. N., Helmchen, U., Mittrücker, H. W., Stahl, R. A. K., & Panzer, U. (2009). CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis. J IMMUNOL, 183(7), 4693-4704. [7]. http://www.ncbi.nlm.nih.gov/pubmed/19734217?dopt=Citation

Vancouver

Steinmetz O, Turner JE, Paust H-J, Lindner M, Peters A, Heiss K et al. CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis. J IMMUNOL. 2009;183(7):4693-4704. 7.

Bibtex

@article{5721dfbfd7f54bda89f23629229cea78,
title = "CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis.",
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.",
author = "Oliver Steinmetz and Turner, {Jan Eric} and Hans-Joachim Paust and Matthias Lindner and Anett Peters and Kirstin Heiss and Joachim Velden and Helmut Hopfer and Susanne Fehr and Thorsten Krieger and Catherine Meyer-Schwesinger and Meyer, {Tobias N} and Udo Helmchen and Mittr{\"u}cker, {Hans Willi} and Stahl, {Rolf A.K.} and Ulf Panzer",
year = "2009",
language = "Deutsch",
volume = "183",
pages = "4693--4704",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

RIS

TY - JOUR

T1 - CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis.

AU - Steinmetz, Oliver

AU - Turner, Jan Eric

AU - Paust, Hans-Joachim

AU - Lindner, Matthias

AU - Peters, Anett

AU - Heiss, Kirstin

AU - Velden, Joachim

AU - Hopfer, Helmut

AU - Fehr, Susanne

AU - Krieger, Thorsten

AU - Meyer-Schwesinger, Catherine

AU - Meyer, Tobias N

AU - Helmchen, Udo

AU - Mittrücker, Hans Willi

AU - Stahl, Rolf A.K.

AU - Panzer, Ulf

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 183

SP - 4693

EP - 4704

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 7

M1 - 7

ER -