| First Author | Eggenhofer E | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 1 | Pages | 480-7 |
| PubMed ID | 23740948 | Mgi Jnum | J:205348 |
| Mgi Id | MGI:5544667 | Doi | 10.4049/jimmunol.1202975 |
| Citation | Eggenhofer E, et al. (2013) Unconventional RORgammat+ T cells drive hepatic ischemia reperfusion injury. J Immunol 191(1):480-7 |
| abstractText | 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 RORgammat(+) T cells. We found that unconventional CD27(-)gammadeltaTCR(+) and CD4(-)CD8(-) double-negative T cells are the major RORgammat-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 RORgammat, as highlighted by the fact that a genetic deficiency for RORgammat, or its therapeutic antagonization via digoxin, is protective against hepatic IRI. Therefore, identification of CD27(-)gammadeltaTCR(+) and CD4(-)CD8(-) double-negative T cells as the major source of IL-17A via RORgammat in hepatic IRI opens new therapeutic options to improve liver transplantation outcomes. |
