title: PPARdelta is a type 1 IFN target gene and inhibits apoptosis in T cells.
abstract: Peroxisome proliferator-activated receptor beta/delta (PPARdelta) is a nuclear hormone receptor regulating diverse biological processes, including beta-oxidation of fatty acid and epithelial cell differentiation. To date, the role of PPARdelta in the immune system has not been thoroughly studied. Here, we show that PPARdelta is expressed in activated human T cells purified from peripheral blood as well as in T cells isolated from affected psoriasis skin lesions. PPARdelta is induced in T cells on stimulation with type 1 IFN. Functionally, PPARdelta enhances proliferation of primary T cells and blocks apoptosis induced by type 1 IFN and by serum deprivation. We show that these cellular functions are mediated by the activation of extracellular signal-regulated kinase1/2 signaling. Our results (1) establish a direct molecular link between type 1 IFN signaling and PPARdelta, (2) define a functional role for PPARdelta in human T cells, and (3) suggest that the induction of PPARdelta by type 1 IFN contributes to the persistence of activated T cells in psoriasis skin lesions.
authors.affiliation: Department of Biology, Free University of Berlin, Berlin, Germany.
authors.forename: Nadya
authors.initials: N
authors.lastname: al Yacoub
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Romanowska
authors.forename: Sybille
authors.initials: S
authors.lastname: Krauss
authors.forename: Susann
authors.initials: S
authors.lastname: Schweiger
authors.forename: John
authors.initials: J
authors.lastname: Foerster
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001706:Biopsy; D049109:Cell Proliferation; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D007370:Interferon Type I; D047494:PPAR delta; D019014:fas Receptor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3