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Régulation de la quiescence et de la migration des lymphocytes T par Fam65b, une nouvelle cible transcriptionnelle de FOX01

Abstract : T cells continually sense numerous soluble and cellular signals, which determine their behavior and differentiation pattern. At the steady state, lymphocytes properties rely on a specific network, in which FoxOs transcription factors play a central role. Indeed, FoxOs-induced transcriptome is involved in the maintenance of T cell quiescence and circulation.We identified a new transcriptional target of FoxO1 named Fam65b. We show that Fam65b acts as a brake on T lymphocyte activation downstream of the T cell receptor. Functionally, we demonstrate that Fam65b negatively regulates the threshold of T cell activation downstream of TCR or CCR7 stimulation. These characteristics allow a more efficient secondary response as Fam65b expression is inhibited. Physiologically, the lower expression of Fam65b in memory T cells compared to naïve T cells takes part in their enhanced reactivity. This suggests that Fam65b could be a functional marker of memory T cells. Finally, we demonstrated that the role of Fam65b is mediated by an inhibition of RhoA activity. Therefore, Fam65b is a regulator of T cell quiescence and migration. Because he regulates the activity of RhoA, Fam65b constitutes a functional link between two major families of proteins which control T cell physiology: Rho GTPases and FoxOs.
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Quitterie Largeteau. Régulation de la quiescence et de la migration des lymphocytes T par Fam65b, une nouvelle cible transcriptionnelle de FOX01. Médecine humaine et pathologie. Université René Descartes - Paris V, 2012. Français. ⟨NNT : 2012PA05T040⟩. ⟨tel-00781901⟩

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