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

Isabelle Mothe-Satney, Joseph Murdaca, Brigitte Sibille, Anne Sophie Rousseau, Raphaëlle Squillace, Gwenaëlle Le Menn, Akila Rekima, Frederic Larbret, Juline Pelé, Valérie Verhasselt, Paul A. Grimaldi, Jaap G. Neels

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 β (PPARβ) increases fatty acid oxidation in T cells. Furthermore, using both in vivo and in vitro models, we demonstrate that PPARβ 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 PPARβ 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 αβ T cells that are derived from DN4 thymocytes are dramatically decreased in peripheral lymphoid tissues, while the 3 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.

Original languageEnglish
Article number34317
Number of pages12
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 29 Sep 2016
Externally publishedYes

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