Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis

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Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis. / Gieseck III, Richard L.; Ramalingam, Thirumalai; Hart, Kevin M.; Vannella, Kevin M.; Cantu, David A.; Lu, Wei-Yu; Ferreira-Gonzalez, Sofia; Forbes, Stuart J.; Vallier, Ludovic; Wynn, Thomas A.

In: Immunity, Vol. 45, No. 1, 19.07.2016, p. 145-158.

Research output: Contribution to journalArticle

Harvard

Gieseck III, RL, Ramalingam, T, Hart, KM, Vannella, KM, Cantu, DA, Lu, W-Y, Ferreira-Gonzalez, S, Forbes, SJ, Vallier, L & Wynn, TA 2016, 'Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis', Immunity, vol. 45, no. 1, pp. 145-158. https://doi.org/10.1016/j.immuni.2016.06.009

APA

Gieseck III, R. L., Ramalingam, T., Hart, K. M., Vannella, K. M., Cantu, D. A., Lu, W-Y., Ferreira-Gonzalez, S., Forbes, S. J., Vallier, L., & Wynn, T. A. (2016). Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis. Immunity, 45(1), 145-158. https://doi.org/10.1016/j.immuni.2016.06.009

Vancouver

Author

Gieseck III, Richard L. ; Ramalingam, Thirumalai ; Hart, Kevin M. ; Vannella, Kevin M. ; Cantu, David A. ; Lu, Wei-Yu ; Ferreira-Gonzalez, Sofia ; Forbes, Stuart J. ; Vallier, Ludovic ; Wynn, Thomas A. / Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis. In: Immunity. 2016 ; Vol. 45, No. 1. pp. 145-158.

Bibtex

@article{f0d5d297fd234c7ca2bf6cfda143c194,
title = "Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis",
abstract = "Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis.",
author = "{Gieseck III}, {Richard L.} and Thirumalai Ramalingam and Hart, {Kevin M.} and Vannella, {Kevin M.} and Cantu, {David A.} and Wei-Yu Lu and Sofia Ferreira-Gonzalez and Forbes, {Stuart J.} and Ludovic Vallier and Wynn, {Thomas A.}",
year = "2016",
month = jul
day = "19",
doi = "10.1016/j.immuni.2016.06.009",
language = "English",
volume = "45",
pages = "145--158",
journal = "Immunity",
issn = "1074-7613",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis

AU - Gieseck III, Richard L.

AU - Ramalingam, Thirumalai

AU - Hart, Kevin M.

AU - Vannella, Kevin M.

AU - Cantu, David A.

AU - Lu, Wei-Yu

AU - Ferreira-Gonzalez, Sofia

AU - Forbes, Stuart J.

AU - Vallier, Ludovic

AU - Wynn, Thomas A.

PY - 2016/7/19

Y1 - 2016/7/19

N2 - Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis.

AB - Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis.

U2 - 10.1016/j.immuni.2016.06.009

DO - 10.1016/j.immuni.2016.06.009

M3 - Article

VL - 45

SP - 145

EP - 158

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 1

ER -