Nuclear Receptor Peroxisome Proliferator-activated Receptor Alpha (PPARalpha) is Expressed in Resting Murine Lymphocytes. The PPARalpha 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. PPARalpha and PPARgamma ligands have been demonstrated to exert anti-inflammatory activities in macrophages by repressing the activities of several transcription factors. PPARgamma 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 PPARalpha. PPARalpha represents the predominant isoform expressed in lymphocytes, whereas PPARgamma dominates in all cell types of the myeloid lineage. PPARalpha expression was down-regulated following T-cell activation while PPARgamma expression increased under the same activating conditions. PPARalpha expression in T cells may be regulated by microenvironmental factors, because Peyer's patch T cells expressed far greater levels of PPARalpha than T cells isolated from peripheral lymphoid organs. Exposure to specific ligand determined that PPARalpha in lymphocytes can effectively transactivate a peroxisome proliferator response element reporter construct. PPARalpha's ability to regulate endogenous genes, however, required treatment with histone deacetylase inhibitors. Finally, ligand activation of lymphocyte PPARalpha antagonized NF-kappaB. Our observation that a functional PPARalpha exists within T cells and B lymphocytes suggests an expanding role for this nuclear receptor in cells of the immune system.