PPARδ is a type 1 IFN target gene and inhibits apoptosis in T cells

Peroxisome proliferator-activated receptor beta/delta (PPAR delta) is a nuclear hormone receptor regulating diverse biological processes, including beta-oxidation of fatty acid and epithelial cell differentiation. To date, the role of PPAR delta in the immune system has not been thoroughly studied. Here, we show that PPAR delta is expressed in activated human T cells purified from peripheral blood as well as in T cells isolated from affected psoriasis skin lesions. PPAR delta is induced in T cells on stimulation with type 1 IFN. Functionally, PPAR delta 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 PPAR delta, (2) define a functional role for PPAR delta in human T cells, and (3) suggest that the induction of PPAR delta by type 1 IFN contributes to the persistence of activated T cells in psoriasis skin lesions.