ArticleScience signaling2013
Diacylglycerol kinase ζ limits the generation of natural regulatory T cells.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Cracking HCC: Targeting diacylglycerol kinase eta to tackle therapy resistance and cancer stemness.Hepatology (Baltimore, Md.) · 2025Article
- Diacylglycerol kinase is a keystone regulator of signaling relevant to the pathophysiology of asthma.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: Relevance to Airway Remodeling in Asthma.International journal of molecular sciences · 2022Article
- Manipulation of diacylglycerol and ERK-mediated signaling differentially controls CD8Frontiers in immunology · 2022Article
- RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance.BMC medical genomics · 2021Article
- Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.European journal of immunology · 2020Article
- The role of diacylglycerol kinases in allergic airway disease.Current opinion in pharmacology · 2020Review
- Plasmacytoid Dendritic Cell-driven Induction of Treg Is Strain Specific and Correlates With Spontaneous Acceptance of Kidney Allografts.Transplantation · 2020Article
- Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms.Science signaling · 2019Article
- DGK α and ζ Activities Control TFrontiers in immunology · 2019Article
- Article
- The Balance of Th17 versus Treg Cells in Autoimmunity.International journal of molecular sciences · 2018Review
- Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells.Frontiers in immunology · 2018Review
- Predominant contribution of DGKζ over DGKα in the control of PKC/PDK-1-regulated functions in T cells.Immunology and cell biology · 2017Article
- A TLR9-dependent checkpoint governs B cell responses to DNA-containing antigens.The Journal of clinical investigation · 2017Article
- Molecular checkpoints controlling natural killer cell activation and their modulation for cancer immunotherapy.Experimental & molecular medicine · 2017Review
- Diacylglycerol Kinase ζ Is a Target To Enhance NK Cell Function.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry.The Journal of biological chemistry · 2016Article
- T cell receptor signalling in the control of regulatory T cell differentiation and function.Nature reviews. Immunology · 2016Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Natural regulatory T (nT(reg)) cells are important for maintaining tolerance to self- and foreign antigens, and they are thought to develop from thymocytes that receive strong T cell receptor (TCR)-mediated signals in the thymus. TCR engagement leads to the activation of phospholipase C-γ1, which generates the lipid second messenger diacylglycerol (DAG) from phosphatidylinositol 4,5-bisphosphate. We used mice that lack the ζ isoform of DAG kinase (DGKζ), which metabolizes DAG to terminate its signaling, to enhance TCR-mediated signaling and identify critical signaling events in nT(reg) cell development. Loss of DGKζ resulted in increased numbers of thymic CD25(+)Foxp3(-)CD4(+) nT(reg) cell precursors and Foxp3(+)CD4(+) nT(reg) cells in a cell-autonomous manner. DGKζ-deficient T cells exhibited increased nuclear translocation of the nuclear factor κB subunit c-Rel, as well as enhanced extracellular signal-regulated kinase (ERK) phosphorylation in response to TCR stimulation, suggesting that these downstream pathways may contribute to nT(reg) cell development. Indeed, reducing c-Rel abundance or blocking ERK phosphorylation abrogated the increased generation of nTreg cells by DGKζ-deficient thymocytes. The extent of ERK phosphorylation correlated with TCR-mediated acquisition of Foxp3 in immature thymocytes in vitro. Furthermore, the development of nT(reg) cells was augmented in mice in which ERK activation was selectively enhanced in T cells. Together, these data suggest that DGKζ regulates the development of nT(reg) cells by limiting the extent of activation of the ERK and c-Rel signaling pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.