title: 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-α (DGKα). 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.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, 28049, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Almena
authors.forename: E
authors.initials: E
authors.lastname: Andrada
authors.forename: R
authors.initials: R
authors.lastname: Liebana
authors.forename: I
authors.initials: I
authors.lastname: Merida
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D060168:Thymocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D011948:Receptors, Antigen, T-Cell; D019852:Diacylglycerol Kinase