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Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis

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Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis. / Schwinge, Dorothee; Carambia, Antonella; Quaas, Alexander; Krech, Till; Wegscheid, Claudia; Tiegs, Gisa; Prinz, Immo; Lohse, Ansgar W; Herkel, Johannes; Schramm, Christoph.

In: J IMMUNOL, Vol. 194, No. 6, 15.03.2015, p. 2522-30.

Research output: SCORING: Contribution to journal › Conference abstract in journal › Research › peer-review

Harvard

Schwinge, D, Carambia, A, Quaas, A, Krech, T, Wegscheid, C, Tiegs, G, Prinz, I, Lohse, AW, Herkel, J & Schramm, C 2015, 'Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis', J IMMUNOL, vol. 194, no. 6, pp. 2522-30. https://doi.org/10.4049/jimmunol.1400076

APA

Schwinge, D., Carambia, A., Quaas, A., Krech, T., Wegscheid, C., Tiegs, G., Prinz, I., Lohse, A. W., Herkel, J., & Schramm, C. (2015). Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis. J IMMUNOL, 194(6), 2522-30. https://doi.org/10.4049/jimmunol.1400076

Vancouver

Schwinge D, Carambia A, Quaas A, Krech T, Wegscheid C, Tiegs G et al. Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis. J IMMUNOL. 2015 Mar 15;194(6):2522-30. https://doi.org/10.4049/jimmunol.1400076

Bibtex

@article{96ae8dd3c17141089780170b80e0f356,
title = "Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis",
abstract = "Autoimmune liver diseases predominantly affect women. In this study, we aimed to elucidate how sex affects autoimmune hepatic inflammation. Acute experimental cholangitis was induced by adoptive transfer of OVA-specific CD8(+) T cells into mice, which express the cognate Ag on cholangiocytes. In contrast to previous mouse models of cholangitis, this model displayed a strong sexual dimorphism: female mice developed marked cholangitis, whereas male mice were resistant to cholangitis induction. The recruitment of endogenous CD4(+) T cells, but not transferred CD8(+) T cells into female livers was strongly increased. These cells expressed higher amounts of the proinflammatory cytokine IL-17, which was at least in part responsible for the liver inflammation observed. The recruitment of endogenous CD4(+) T cells was associated with increased expression of the chemokines CXCL-9 and CXCL-10 in female livers. The sex-specific factor responsible for the observed differences was found to be testosterone: male mice could be rendered susceptible to liver inflammation by castration, and testosterone treatment was sufficient to completely suppress liver inflammation in female mice. Accordingly, testosterone treatment of female mice significantly reduced the expression of IL-17A, CXCL-9, and CXCL-10 within the liver. Serum testosterone levels of untreated mice negatively correlated with the IL-17, CXCL-9, and CXCL-10 expression in the liver, further supporting a role for testosterone in hepatic immune homeostasis. In conclusion, testosterone was found to be the major determinant of the observed sexual dimorphism. Further study into the role of testosterone for liver inflammation could lead to novel treatment targets in human autoimmune liver diseases.",
author = "Dorothee Schwinge and Antonella Carambia and Alexander Quaas and Till Krech and Claudia Wegscheid and Gisa Tiegs and Immo Prinz and Lohse, {Ansgar W} and Johannes Herkel and Christoph Schramm",
note = "Copyright {\textcopyright} 2015 by The American Association of Immunologists, Inc.",
year = "2015",
month = mar,
day = "15",
doi = "10.4049/jimmunol.1400076",
language = "English",
volume = "194",
pages = "2522--30",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

RIS

TY - JOUR

T1 - Testosterone Suppresses Hepatic Inflammation by the Downregulation of IL-17, CXCL-9, and CXCL-10 in a Mouse Model of Experimental Acute Cholangitis

AU - Schwinge, Dorothee

AU - Carambia, Antonella

AU - Quaas, Alexander

AU - Krech, Till

AU - Wegscheid, Claudia

AU - Tiegs, Gisa

AU - Prinz, Immo

AU - Lohse, Ansgar W

AU - Herkel, Johannes

AU - Schramm, Christoph

N1 - Copyright © 2015 by The American Association of Immunologists, Inc.

PY - 2015/3/15

Y1 - 2015/3/15

N2 - Autoimmune liver diseases predominantly affect women. In this study, we aimed to elucidate how sex affects autoimmune hepatic inflammation. Acute experimental cholangitis was induced by adoptive transfer of OVA-specific CD8(+) T cells into mice, which express the cognate Ag on cholangiocytes. In contrast to previous mouse models of cholangitis, this model displayed a strong sexual dimorphism: female mice developed marked cholangitis, whereas male mice were resistant to cholangitis induction. The recruitment of endogenous CD4(+) T cells, but not transferred CD8(+) T cells into female livers was strongly increased. These cells expressed higher amounts of the proinflammatory cytokine IL-17, which was at least in part responsible for the liver inflammation observed. The recruitment of endogenous CD4(+) T cells was associated with increased expression of the chemokines CXCL-9 and CXCL-10 in female livers. The sex-specific factor responsible for the observed differences was found to be testosterone: male mice could be rendered susceptible to liver inflammation by castration, and testosterone treatment was sufficient to completely suppress liver inflammation in female mice. Accordingly, testosterone treatment of female mice significantly reduced the expression of IL-17A, CXCL-9, and CXCL-10 within the liver. Serum testosterone levels of untreated mice negatively correlated with the IL-17, CXCL-9, and CXCL-10 expression in the liver, further supporting a role for testosterone in hepatic immune homeostasis. In conclusion, testosterone was found to be the major determinant of the observed sexual dimorphism. Further study into the role of testosterone for liver inflammation could lead to novel treatment targets in human autoimmune liver diseases.

AB - Autoimmune liver diseases predominantly affect women. In this study, we aimed to elucidate how sex affects autoimmune hepatic inflammation. Acute experimental cholangitis was induced by adoptive transfer of OVA-specific CD8(+) T cells into mice, which express the cognate Ag on cholangiocytes. In contrast to previous mouse models of cholangitis, this model displayed a strong sexual dimorphism: female mice developed marked cholangitis, whereas male mice were resistant to cholangitis induction. The recruitment of endogenous CD4(+) T cells, but not transferred CD8(+) T cells into female livers was strongly increased. These cells expressed higher amounts of the proinflammatory cytokine IL-17, which was at least in part responsible for the liver inflammation observed. The recruitment of endogenous CD4(+) T cells was associated with increased expression of the chemokines CXCL-9 and CXCL-10 in female livers. The sex-specific factor responsible for the observed differences was found to be testosterone: male mice could be rendered susceptible to liver inflammation by castration, and testosterone treatment was sufficient to completely suppress liver inflammation in female mice. Accordingly, testosterone treatment of female mice significantly reduced the expression of IL-17A, CXCL-9, and CXCL-10 within the liver. Serum testosterone levels of untreated mice negatively correlated with the IL-17, CXCL-9, and CXCL-10 expression in the liver, further supporting a role for testosterone in hepatic immune homeostasis. In conclusion, testosterone was found to be the major determinant of the observed sexual dimorphism. Further study into the role of testosterone for liver inflammation could lead to novel treatment targets in human autoimmune liver diseases.

U2 - 10.4049/jimmunol.1400076

DO - 10.4049/jimmunol.1400076

M3 - Conference abstract in journal

C2 - 25672751

VL - 194

SP - 2522

EP - 2530

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 6

ER -