Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis.

Hans-Joachim Paust; Jan Eric Turner; Jan-Hendrik Riedel; Erik Disteldorf; Anett Peters; Tilman Schmidt; Christian Krebs; Joachim Velden; Hans Willi Mittrücker; Oliver Steinmetz; Rolf A.K. Stahl; Ulf Panzer

Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis.

Standard

Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis. / Paust, Hans-Joachim ; Turner, Jan Eric ; Riedel, Jan-Hendrik; Disteldorf, Erik; Peters, Anett; Schmidt, Tilman; Krebs, Christian; Velden, Joachim; Mittrücker, Hans Willi ; Steinmetz, Oliver ; Stahl, Rolf A.K.; Panzer, Ulf.

In: KIDNEY INT, Vol. 82, No. 1, 1, 2012, p. 72-83.

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

Harvard

Paust, H-J , Turner, JE , Riedel, J-H, Disteldorf, E, Peters, A, Schmidt, T, Krebs, C, Velden, J, Mittrücker, HW , Steinmetz, O , Stahl, RAK & Panzer, U 2012, 'Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis.', KIDNEY INT, vol. 82, no. 1, 1, pp. 72-83. <http://www.ncbi.nlm.nih.gov/pubmed/22495297?dopt=Citation>

APA

Paust, H-J., Turner, J. E., Riedel, J-H., Disteldorf, E., Peters, A., Schmidt, T., Krebs, C., Velden, J., Mittrücker, H. W., Steinmetz, O., Stahl, R. A. K., & Panzer, U. (2012). Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis. KIDNEY INT, 82(1), 72-83. [1]. http://www.ncbi.nlm.nih.gov/pubmed/22495297?dopt=Citation

Vancouver

Paust H-J , Turner JE , Riedel J-H, Disteldorf E, Peters A, Schmidt T et al. Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis. KIDNEY INT. 2012;82(1):72-83. 1.

Bibtex

@article{28d5dc63411048ac9d86c77978c95654,

title = "Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis.",

abstract = "Th1 and Th17 subtype effector CD4(+) T cells are thought to play a critical role in the pathogenesis of human and experimental crescentic glomerulonephritis. The time course, mechanism, and functions of Th1 and Th17 cell recruitment, and their potential interaction in glomerulonephritis, however, remain to be elucidated. We performed interventional studies using IL-17- and IFN-?-gene-deficient mice, as well as neutralizing antibodies that demonstrated the importance of the Th17-mediated immune response during the early phase of the disease. At a later stage, we found that Th1 cells were critical mediators of renal tissue injury. Early recruitment of IL-17-producing Th17 cells triggered expression of the chemokine CXCL9 in the kidney that drove the infiltration of Th1 cells bearing its receptor CXCR3. At a later stage, Th1 cell-derived IFN-? was found to inhibit local chemokine CCL20 expression, acting through its receptor CCR6 on Th17 cells, thereby limiting the renal Th17 immune response. Thus, our findings provide mechanistic evidence for a cytokine-chemokine-driven feedback loop that orchestrates the observed differential Th1 and Th17 cell infiltration into the inflamed kidney. This contributes to the observed time-dependent function of these two major pathogenic effector CD4(+) T cell subsets in crescentic glomerulonephritis.",

keywords = "Animals, Male, Time Factors, Gene Expression Regulation, Cells, Cultured, Disease Models, Animal, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction, Sheep, Chemokines/genetics/*metabolism, Th1 Cells/*immunology, Homeodomain Proteins/genetics/metabolism, Th17 Cells/*immunology, Spleen/immunology, Adoptive Transfer, *Cell Communication, Antibodies, Neutralizing, Chemokine CCL20/metabolism, Chemokine CXCL9/metabolism, Chemotaxis, Leukocyte, Feedback, Physiological, Glomerulonephritis/genetics/*immunology/pathology, Immunoglobulin G, Interferon-gamma/deficiency/genetics, Interleukin-17/deficiency/genetics, Kidney/*immunology/pathology, Receptors, CCR6/deficiency/genetics, Receptors, CXCR3/deficiency/genetics, Animals, Male, Time Factors, Gene Expression Regulation, Cells, Cultured, Disease Models, Animal, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction, Sheep, Chemokines/genetics/*metabolism, Th1 Cells/*immunology, Homeodomain Proteins/genetics/metabolism, Th17 Cells/*immunology, Spleen/immunology, Adoptive Transfer, *Cell Communication, Antibodies, Neutralizing, Chemokine CCL20/metabolism, Chemokine CXCL9/metabolism, Chemotaxis, Leukocyte, Feedback, Physiological, Glomerulonephritis/genetics/*immunology/pathology, Immunoglobulin G, Interferon-gamma/deficiency/genetics, Interleukin-17/deficiency/genetics, Kidney/*immunology/pathology, Receptors, CCR6/deficiency/genetics, Receptors, CXCR3/deficiency/genetics",

author = "Hans-Joachim Paust and Turner, {Jan Eric} and Jan-Hendrik Riedel and Erik Disteldorf and Anett Peters and Tilman Schmidt and Christian Krebs and Joachim Velden and Mittr{\"u}cker, {Hans Willi} and Oliver Steinmetz and Stahl, {Rolf A.K.} and Ulf Panzer",

year = "2012",

language = "English",

volume = "82",

pages = "72--83",

journal = "KIDNEY INT",

issn = "0085-2538",

publisher = "NATURE PUBLISHING GROUP",

number = "1",

}

RIS

TY - JOUR

T1 - Chemokines play a critical role in the cross-regulation of Th1 and Th17 immune responses in murine crescentic glomerulonephritis.

AU - Paust, Hans-Joachim

AU - Turner, Jan Eric

AU - Riedel, Jan-Hendrik

AU - Disteldorf, Erik

AU - Peters, Anett

AU - Schmidt, Tilman

AU - Krebs, Christian

AU - Velden, Joachim

AU - Mittrücker, Hans Willi

AU - Steinmetz, Oliver

AU - Stahl, Rolf A.K.

AU - Panzer, Ulf

PY - 2012

Y1 - 2012

N2 - Th1 and Th17 subtype effector CD4(+) T cells are thought to play a critical role in the pathogenesis of human and experimental crescentic glomerulonephritis. The time course, mechanism, and functions of Th1 and Th17 cell recruitment, and their potential interaction in glomerulonephritis, however, remain to be elucidated. We performed interventional studies using IL-17- and IFN-?-gene-deficient mice, as well as neutralizing antibodies that demonstrated the importance of the Th17-mediated immune response during the early phase of the disease. At a later stage, we found that Th1 cells were critical mediators of renal tissue injury. Early recruitment of IL-17-producing Th17 cells triggered expression of the chemokine CXCL9 in the kidney that drove the infiltration of Th1 cells bearing its receptor CXCR3. At a later stage, Th1 cell-derived IFN-? was found to inhibit local chemokine CCL20 expression, acting through its receptor CCR6 on Th17 cells, thereby limiting the renal Th17 immune response. Thus, our findings provide mechanistic evidence for a cytokine-chemokine-driven feedback loop that orchestrates the observed differential Th1 and Th17 cell infiltration into the inflamed kidney. This contributes to the observed time-dependent function of these two major pathogenic effector CD4(+) T cell subsets in crescentic glomerulonephritis.

AB - Th1 and Th17 subtype effector CD4(+) T cells are thought to play a critical role in the pathogenesis of human and experimental crescentic glomerulonephritis. The time course, mechanism, and functions of Th1 and Th17 cell recruitment, and their potential interaction in glomerulonephritis, however, remain to be elucidated. We performed interventional studies using IL-17- and IFN-?-gene-deficient mice, as well as neutralizing antibodies that demonstrated the importance of the Th17-mediated immune response during the early phase of the disease. At a later stage, we found that Th1 cells were critical mediators of renal tissue injury. Early recruitment of IL-17-producing Th17 cells triggered expression of the chemokine CXCL9 in the kidney that drove the infiltration of Th1 cells bearing its receptor CXCR3. At a later stage, Th1 cell-derived IFN-? was found to inhibit local chemokine CCL20 expression, acting through its receptor CCR6 on Th17 cells, thereby limiting the renal Th17 immune response. Thus, our findings provide mechanistic evidence for a cytokine-chemokine-driven feedback loop that orchestrates the observed differential Th1 and Th17 cell infiltration into the inflamed kidney. This contributes to the observed time-dependent function of these two major pathogenic effector CD4(+) T cell subsets in crescentic glomerulonephritis.

KW - Animals

KW - Male

KW - Time Factors

KW - Gene Expression Regulation

KW - Cells, Cultured

KW - Disease Models, Animal

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Signal Transduction

KW - Sheep

KW - Chemokines/genetics/metabolism

KW - Th1 Cells/immunology

KW - Homeodomain Proteins/genetics/metabolism

KW - Th17 Cells/immunology

KW - Spleen/immunology

KW - Adoptive Transfer

KW - Cell Communication

KW - Antibodies, Neutralizing

KW - Chemokine CCL20/metabolism

KW - Chemokine CXCL9/metabolism

KW - Chemotaxis, Leukocyte

KW - Feedback, Physiological

KW - Glomerulonephritis/genetics/immunology/pathology

KW - Immunoglobulin G

KW - Interferon-gamma/deficiency/genetics

KW - Interleukin-17/deficiency/genetics

KW - Kidney/immunology/pathology

KW - Receptors, CCR6/deficiency/genetics

KW - Receptors, CXCR3/deficiency/genetics