PPARdelta is a type 1 IFN target gene and inhibits apoptosis in T cells.
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.
al Yacoub
Nadya
N
Department of Biology, Free University of Berlin, Berlin, Germany.
Romanowska
Malgorzata
M
Krauss
Sybille
S
Schweiger
Susann
S
Foerster
John
J
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
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