The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis

Abstract

Peroxisome proliferator-activated receptor (PPAR)-γ is a nuclear hormone receptor that serves as a trans factor to regulate lipid metabolism. Intense interest is focused on PPAR-γ and its ligands owing to its putative role in adipocyte differentiation. Little is known, however, about the functions of PPAR-γ in the immune system, especially in T lymphocytes. We demonstrate that both naive and activated ovalbumin-specific T cells from DO11.10-transgenic mice express PPAR-γ mRNA and protein. In order to determine the function of PPAR-γ, T cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin or antigen and antigen-presenting cells. Simultaneous exposure to PPAR-γ ligands (e.g. 15-deoxy-Δ 12,14-prostaglandin J2, troglitazone) showed drastic inhibition of proliferation and significant decreases in cell viability. The decrease in cell viability was due to apoptosis of the T lymphocytes, and occurred only when cells were treated with PPAR-γ, and not PPAR-α agonists, revealing specificity of this response for PPAR-γ. These observations suggest that PPAR-γ agonists play an important role in regulating T cell-mediated immune responses by inducing apoptosis. T cell death via PPAR-γ ligation may act as a potent anti-inflammatory signal in the immune system, and ligands could possibly be used to control disorders in which excessive inflammation occurs.