Eggenhofer, Elke and Rovira, Jordi and Sabet-Baktach, Manije and Groell, Anja and Scherer, Marcus N. and Dahlke, Marc-Hendrik and Farkas, Stefan A. and Loss, Martin and Koehl, Gudrun E. and Lang, Sven A. and Melter, Michael and Schlitt, Hans J. and Geissler, Edward K. and Kroemer, Alexander (2013) Unconventional ROR gamma t(+) T Cells Drive Hepatic Ischemia Reperfusion Injury. JOURNAL OF IMMUNOLOGY, 191 (1). pp. 480-487. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)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 ROR gamma t(+) T cells. We found that unconventional CD27(-)gamma delta TCR+ and CD4(-)CD8(-) double-negative T cells are the major ROR gamma t-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 ROR gamma t, as highlighted by the fact that a genetic deficiency for RORgt, or its therapeutic antagonization via digoxin, is protective against hepatic IRI. Therefore, identification of CD27(-)gamma delta TCR+ and CD4(-)CD8(-) double-negative T cells as the major source of IL-17A via ROR gamma t in hepatic IRI opens new therapeutic options to improve liver transplantation outcomes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIVER ISCHEMIA/REPERFUSION INJURY; TISSUE INFLAMMATION; MICE; RAT; DIFFERENTIATION; T(H)17; MOUSE; MODEL; IL-17; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Apr 2020 09:01 |
| Last Modified: | 07 Apr 2020 09:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16454 |
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