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.

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