Research ArticleLIVER INJURY

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

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Science Translational Medicine  03 Feb 2021:
Vol. 13, Issue 579, eabb6576
DOI: 10.1126/scitranslmed.abb6576

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Engaging eosinophils against liver injury

Hepatic ischemia and reperfusion (IR) injury after liver transplant can cause allograft dysfunction and rejection. To investigate the pathogenesis of hepatic IR injury and to identify potential therapeutic targets, Wang et al. characterized the immune cells that accumulate in livers within hours after transplantation in humans. The authors found recruitment of eosinophils, a granulocyte population thought to play a role in immune responses to parasites and, more recently, promote wound healing. Through a series of eosinophil transfers and depletions in mice, the authors demonstrated that eosinophils are hepatoprotective and promote healthy liver function after IR injury by producing interleukin-13 (IL-13) in response to IL-33 signaling. Together, these findings suggest that strategies to promote eosinophil recruitment to the liver may be effective in protecting against hepatic IR 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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