title: Unconventional RORγt+ T cells drive hepatic ischemia reperfusion injury.
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.
authors.affiliation: Department of Surgery, University Hospital Regensburg, University of Regensburg, 93053 Regensburg, Germany. elke.eggenhofer@ukr.de
authors.forename: Elke
authors.initials: E
authors.lastname: Eggenhofer
authors.forename: Jordi
authors.initials: J
authors.lastname: Rovira
authors.forename: Manije
authors.initials: M
authors.lastname: Sabet-Baktach
authors.forename: Anja
authors.initials: A
authors.lastname: Groell
authors.forename: Marcus N
authors.initials: MN
authors.lastname: Scherer
authors.forename: Marc-Hendrik
authors.initials: MH
authors.lastname: Dahlke
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Farkas
authors.forename: Martin
authors.initials: M
authors.lastname: Loss
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Koehl
authors.forename: Sven A
authors.initials: SA
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Melter
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Alexander
authors.initials: A
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017930:Genes, Reporter; D006520:Hepatitis, Animal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000502:physiology*; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D057132:Nuclear Receptor Subfamily 1, Group F, Member 3