title: A novel T(H)17-type cell is rapidly increased in the liver in response to acetaminophen-induced liver injury: T(H)17 cells and the innate immune response.
abstract: Helper T (T(H)) cells are an important part of the adaptive immune system. It is hypothesized that one type of helper T-cell, T(H)17 cells, play an important role in idiosyncratic drug-induced liver failure, and it was found that interleukin (IL)-17, the signature cytokine of T(H)17 cells, was elevated in most patients with idiosyncratic drug-induced liver failure. However, it was also found that IL-17 was elevated in some patients with acetaminophen (APAP)-induced liver failure. It is unlikely that APAP-induced liver failure is mediated by the adaptive immune system, but there are other cells such as macrophages and natural killer (NK) cells that also produce IL-17. Therefore, the phenotype of cells that produce IL-17 was studied in a mouse model of APAP-induced liver toxicity. To the authors' surprise, it was found that most of the IL-17 producing cells in the liver were T(H)17 cells, and they were increased within hours of APAP treatment. This is too fast for a response of the adaptive immune system. These data suggest that T(H)17 cells can be part of the innate immune response; however, it is unclear what role they play in the pathogenesis of APAP-induced hepatotoxicity.
authors.affiliation: Immunotoxicology CoE, Drug Safety Research and Development, Pfizer, Inc. Groton, CT, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhu
authors.forename: Jack
authors.initials: J
authors.lastname: Uetrecht
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects* / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen