A role for Peroxisome Proliferator-Activated Receptor Beta in T cell development

Metabolism plays an important role in T cell biology and changes in metabolism drive T cell differentiation and fate. Most research on the role of metabolism in T lymphocytes focuses on mature T cells while only few studies have investigated the role of metabolism in T cell development. In this study, we report that activation or overexpression of the transcription factor Peroxisome Proliferator-Activated Receptor beta (PPAR beta) increases fatty acid oxidation in T cells. Furthermore, using both in vivo and in vitro models, we demonstrate that PPAR beta activation/overexpression inhibits thymic T cell development by decreasing proliferation of CD4-CD8-double-negative stage 4 (DN4) thymocytes. These results support a model where PPAR beta activation/overexpression favours fatty acid-instead of glucose-oxidation in developing T cells, thereby hampering the proliferative burst normally occurring at the DN4 stage of T cell development. As a consequence, the alpha beta T cells that are derived from DN4 thymocytes are dramatically decreased in peripheral lymphoid tissues, while the gamma delta T cell population remains untouched. This is the first report of a direct role for a member of the PPAR family of nuclear receptors in the development of T cells.