TY - JOUR
T1 - Eosinophils attenuate hepatic ischemia-reperfusion injury in mice through ST2-dependent IL-13 production
AU - Wang, Yaochun
AU - Yang, Yang
AU - Wang, Meng
AU - Wang, Shuhong
AU - Jeong, Jong Min
AU - Xu, Long
AU - Wen, Yankai
AU - Emontzpohl, Christoph
AU - Atkins, Constance Lynn
AU - Duong, Kevin
AU - Moreno, Nicolas F.
AU - Yuan, Xiaoyi
AU - Hall, David R.
AU - Dar, Wasim
AU - Feng, Dechun
AU - Gao, Bin
AU - Xu, Yong
AU - Czigany, Zoltan
AU - Colgan, Sean P.
AU - Bynon, J. Steve
AU - Akira, Shizuo
AU - Brown, Jared M.
AU - Eltzschig, Holger K.
AU - Jacobsen, Elizabeth A.
AU - Ju, Cynthia
N1 - Publisher Copyright:
Copyright © 2021 The Authors.
PY - 2021/2/3
Y1 - 2021/2/3
N2 - Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wildtype mice. Mechanistic studies combining genetic and adoptive transfer approaches identified a critical role of suppression of tumorigenicity (ST2)-dependent production of interleukin-13 by eosinophils in the hepatoprotection against ischemia-reperfusion-induced injury. Together, these data provide insight into a mechanism of eosinophil-mediated liver protection that could serve as a therapeutic target to improve outcomes of patients undergoing liver transplantation.
AB - Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wildtype mice. Mechanistic studies combining genetic and adoptive transfer approaches identified a critical role of suppression of tumorigenicity (ST2)-dependent production of interleukin-13 by eosinophils in the hepatoprotection against ischemia-reperfusion-induced injury. Together, these data provide insight into a mechanism of eosinophil-mediated liver protection that could serve as a therapeutic target to improve outcomes of patients undergoing liver transplantation.
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U2 - 10.1126/scitranslmed.abb6576
DO - 10.1126/scitranslmed.abb6576
M3 - Article
C2 - 33536281
AN - SCOPUS:85101046965
SN - 1946-6234
VL - 13
JO - Science translational medicine
JF - Science translational medicine
IS - 579
M1 - eabb6576
ER -