Publication Date
2-3-2021
Journal
Science Translational Medicine
DOI
10.1126/scitranslmed.abb6576
PMID
33536281
PMCID
PMC8167890
PubMedCentral® Posted Date
6-1-2021
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Adoptive Transfer, Animals, Eosinophils, Humans, Interleukin-13, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Reperfusion Injury
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.
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