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.
UR - https://www.research.ed.ac.uk/portal/en/publications/interleukin13-activates-distinct-cellular-pathways-leading-to-ductular-reaction-steatosis-and-fibrosis(2d4ea5e7-1635-48fd-a112-fb2098ca9704).html
U2 - 10.1016/j.immuni.2016.06.009
DO - 10.1016/j.immuni.2016.06.009
M3 - Article
SN - 1074-7613
VL - 45
SP - 145
EP - 158
JO - Immunity
JF - Immunity
IS - 1
ER -