Nuclear Receptor Peroxisome Proliferator-activated Receptor (PPAR) Is Expressed in Resting Murine Lymphocytes

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 NF-B. 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.