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Diacylglycerol metabolism attenuates T-cell receptor signaling and alters thymocyte differentiation.

ABSTRACT: Diacylglycerol (DAG) metabolism has a critical function in Ras-regulated functions in mature T cells, but causal data linking defects in DAG-based signals with altered thymus development are missing. To study the effect of increased DAG metabolism in T-cell development, we engineered a membrane-targeted constitutive active version of DAG kinase-? (DGK?). We show that transgenic expression of constitutive active DGK leads to developmental defects in T cells, with a marked accumulation of immature CD8 thymocytes and a reduction in positive selected populations. These alterations are reflected in the periphery by a CD4/CD8 cell imbalance and general T-cell lymphopenia. The results link DAG metabolism to T-cell homeostasis, and show that correctly controlled generation and consumption of this lipid at the plasma membrane ensure T-cell passage through quality-control checkpoints during differentiation.

SUBMITTER: Almena M

PROVIDER: S-EPMC3847306 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Diacylglycerol metabolism attenuates T-cell receptor signaling and alters thymocyte differentiation.

Almena M M Andrada E E Liebana R R Merida I I

Cell death & disease 20131107

Diacylglycerol (DAG) metabolism has a critical function in Ras-regulated functions in mature T cells, but causal data linking defects in DAG-based signals with altered thymus development are missing. To study the effect of increased DAG metabolism in T-cell development, we engineered a membrane-targeted constitutive active version of DAG kinase-α (DGKα). We show that transgenic expression of constitutive active DGK leads to developmental defects in T cells, with a marked accumulation of immature ...[more]

PMID: 24201811

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