Eosinophils attenuate hepatic ischemia-reperfusion injury in mice through ST2-dependent IL-13 production.

Affiliation

Wang Y(1)(2), Yang Y(1), Wang M(1), Wang S(1), Jeong JM(1), Xu L(1), Wen Y(1), Emontzpohl C(1), Atkins CL(1), Duong K(1), Moreno NF(1), Yuan X(1), Hall DR(3), Dar W(3), Feng D(4), Gao B(4), Xu Y(5)(6), Czigany Z(7), Colgan SP(8), Bynon JS(3), Akira S(9), Brown JM(10), Eltzschig HK(1), Jacobsen EA(11), Ju C(12).
Author information:
(1)Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
(2)Center for Translational Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
(3)Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
(4)Laboratory of Liver Disease, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
(5)Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
(6)Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
(7)Department of Surgery and Transplantation, Faculty of Medicine, University Hospital RWTH Aachen, Aachen 52074, Germany.
(8)Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
(9)Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
(10)School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
(11)Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA.
(12)Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. [Email]

Abstract

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.