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J Immunol. 2013 Jul 1;191(1):480-7. doi: 10.4049/jimmunol.1202975. Epub 2013 Jun 5.

Unconventional RORγt+ T cells drive hepatic ischemia reperfusion injury.

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  • 1Department of Surgery, University Hospital Regensburg, University of Regensburg, 93053 Regensburg, Germany. elke.eggenhofer@ukr.de

Abstract

An emerging body of evidence suggests a pivotal role of CD3(+) T cells in mediating early ischemia reperfusion injury (IRI). However, the precise phenotype of T cells involved and the mechanisms underlying such T cell-mediated immune responses in IRI, as well as their clinical relevance, are poorly understood. In this study, we investigated early immunological events in a model of partial warm hepatic IRI in genetically targeted mice to study the precise pathomechanistic role of RORγt(+) T cells. We found that unconventional CD27(-)γδTCR(+) and CD4(-)CD8(-) double-negative T cells are the major RORγt-expressing effector cells in hepatic IRI that play a mechanistic role by being the main source of IRI-mediating IL-17A. We further show that unconventional IRI-mediating T cells are contingent on RORγt, as highlighted by the fact that a genetic deficiency for RORγt, or its therapeutic antagonization via digoxin, is protective against hepatic IRI. Therefore, identification of CD27(-)γδTCR(+) and CD4(-)CD8(-) double-negative T cells as the major source of IL-17A via RORγt in hepatic IRI opens new therapeutic options to improve liver transplantation outcomes.

PMID:
23740948
[PubMed - indexed for MEDLINE]
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