Open AccessEosinophils attenuate hepatic ischemia-reperfusion injury in mice through ST2-dependent IL-13 production
Author(s) -
Yao-Chun Wang,
Yang Yang,
Meng Wang,
Shuhong Wang,
Jong Min Jeong,
Long Xu,
Yankai Wen,
Christoph Emontzpohl,
Constance L. Atkins,
Kevin Duong,
Nicolas F. Moreno,
Xiaoyi Yuan,
David R. Hall,
Wasim Dar,
Dechun Feng,
Bin Gao,
Yong Xu,
Zoltán Czigány,
Sean P. Colgan,
John S. By,
Shizuo Akira,
Jared M. Brown,
Holger K. Eltzschig,
Elizabeth A. Jacobsen,
Cynthia Ju
Publication year - 2021
Publication title -
science translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.819
H-Index - 216
eISSN - 1946-6242
pISSN - 1946-6234
DOI - 10.1126/scitranslmed.abb6576
Subject(s) - eosinophil , adoptive cell transfer , medicine , reperfusion injury , liver transplantation , immunology , ischemia , liver injury , transplantation , immune system , pathology , t cell , pharmacology , asthma
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 wild-type 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.