Nuclear Receptor Peroxisome Proliferator-activated Receptor (PPAR ) Is Expressed in Resting Murine Lymphocytes THE PPAR IN T AND B LYMPHOCYTES IS BOTH TRANSACTIVATION AND TRANSREPRESSION COMPETENT*

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear hormone receptor superfamily. PPAR and PPAR ligands have been demonstrated to exert anti-inflammatory activities in macrophages by repressing the activities of several transcription factors. PPAR is expressed in T lymphocytes and may play a role in cytokine production, cellular proliferation, and susceptibility to apoptosis. Herein, we demonstrate that T and B lymphocytes constitutively express PPAR . PPAR represents the predominant isoform expressed in lymphocytes, whereas PPAR dominates in all cell types of the myeloid lineage. PPAR expression was down-regulated following T-cell activation while PPAR expression increased under the same activating conditions. PPAR expression in T cells may be regulated by microenvironmental factors, because Peyer’s patch T cells expressed far greater levels of PPAR than T cells isolated from peripheral lymphoid organs. Exposure to specific ligand determined that PPAR in lymphocytes can effectively transactivate a peroxisome proliferator response element reporter construct. PPAR ’s ability to regulate endogenous genes, however, required treatment with histone deacetylase inhibitors. Finally, ligand activation of lymphocyte PPAR antagonized NFB. Our observation that a functional PPAR exists within T cells and B lymphocytes suggests an expanding role for this nuclear receptor in cells of the immune system.