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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #395859
Research Project: Molecular, Cellular, and Regulatory Aspects of Obesity Development

Location: Children's Nutrition Research Center

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

Author
item WANG, YAOCHUN - University Of Texas Health Science Center
item YANG, YANG - University Of Texas Health Science Center
item WANG, MENG - University Of Texas Health Science Center
item WANG, SHUHONG - University Of Texas Health Science Center
item JEONG, JONG-MIN - University Of Texas Health Science Center
item XU, LONG - University Of Texas Health Science Center
item WEN, YANKAI - University Of Texas Health Science Center
item EMONTZPOH, CHRISTOPH - University Of Texas Health Science Center
item ATKINS, CONSTANCE - University Of Texas Health Science Center
item DUONG, KEVIN - University Of Texas Health Science Center
item MORENO, NICOLAS - University Of Texas Health Science Center
item YUAN, XIAOYI - University Of Texas Health Science Center
item HALL, DAVID - University Of Texas Health Science Center
item DAR, WASIM - University Of Texas Health Science Center
item FENG, DECHUN - National Institutes Of Health (NIH)
item GAO, BIN - National Institutes Of Health (NIH)
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item CZIGANY, ZOLTAN - Aachen University
item COLGAN, SEAN - University Of Colorado
item BYNON, STEVE - University Of Texas Health Science Center
item AKIRA, SHIZUO - Osaka City University
item BROWN, JARED - University Of Colorado
item ELTZSCHIG, HOLGER - University Of Texas Health Science Center
item JACOBSEN, ELIZABETH - Mayo Clinic College Of Medicine
item JU, CYNTHIA - University Of Texas Health Science Center

Submitted to: Science Translational Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/12/2021
Publication Date: 2/3/2021
Citation: Wang, Y., Yang, Y., Wang, M., Wang, S., Jeong, J., Xu, L., Wen, Y., Emontzpoh, C., Atkins, C., Duong, K., Moreno, N., Yuan, X., Hall, D., Dar, W., Feng, D., Gao, B., Xu, Y., Czigany, Z., Colgan, S., Bynon, S., Akira, S., Brown, J., Eltzschig, H., Jacobsen, E., Ju, C. 2021. Eosinophils attenuate hepatic ischemia-reperfusion injury in mice through ST2-dependent IL-13 production. Science Translational Medicine. 13(579). https://doi.org/10.1126/scitranslmed.abb6576.
DOI: https://doi.org/10.1126/scitranslmed.abb6576

Interpretive Summary: Eosinophils, a type of cell involved in immune response, has been found to rapidly accumulate in human liver grafts after liver transplantation. In eosinophil-deficient mice, the transplantation of eosinophils reduces liver injury. Here we found the mechanism by which eosinophils may protect against liver injury. Through a combination of genetic and adoptive transfer approaches, we identified that eosinophils have a critical role in the suppression of tumorigenicity-dependent production of the cytokine interleukin-13. This work provides a therapeutic target that may improve outcomes of individuals undergoing a liver transplant.

Technical 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.