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 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 γδ 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.
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Isabelle
I
Mothe-Satney
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Joseph
J
Murdaca
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Brigitte
B
Sibille
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Anne-Sophie
AS
Rousseau
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Raphaëlle
R
Squillace
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Gwenaëlle
G
Le Menn
Université Côte d'Azur, EA 6302 Tolérance Immunitaire, Nice, France.
Akila
A
Rekima
Université Côte d'Azur, EA 6302 Tolérance Immunitaire, Nice, France.
Frederic
F
Larbret
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Juline
J
Pelé
Université Côte d'Azur, EA 6302 Tolérance Immunitaire, Nice, France.
Valérie
V
Verhasselt
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Paul A
PA
Grimaldi
Université Côte d'Azur, Inserm, C3M, France.|INSERM U1065, Mediterranean Center of Molecular Medicine (C3M), Team 9 "Adaptive responses to immuno-metabolic dysregulations", Nice, France.
Jaap G
JG
Neels
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