ArticleScience translational medicine2016
Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- Endogenous tracking reveals paralog-specific targets for phosphatidic acid generation during phospholipase C signaling in living cells.The Journal of biological chemistry · 2026Article
- Article
- PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling.Cell death & disease · 2026Article
- Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.Medicinal research reviews · 2026Review
- X-linked lymphoproliferative disease type 1 (XLP1) due to a "de novo" missense SH2D1A Hemizygous Mutation Leading to Predominantly Antibody Deficiency.Research square · 2025Article
- X-linked lymphoproliferative disease type 1: a clinical and genetic update.Frontiers in immunology · 2025Review
- Murine Models of Familial Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Role of Diacylglycerol Kinases in Acute Myeloid Leukemia.Biomedicines · 2023Article
- When to suspect inborn errors of immunity in Epstein-Barr virus-related lymphoproliferative disorders.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023Review
- Molecular and temporal control of restimulation-induced cell death (RICD) in T lymphocytes.Frontiers in cell death · 2023Article
- Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction.Frontiers in immunology · 2023Article
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- Restimulation-Induced Cell Death (RICD): Methods for Modeling, Investigating, and Quantifying RICD Sensitivity in Primary Human T Cells via Flow Cytometric Analysis.Bio-protocol · 2022Article
- Genome Editing With TALEN, CRISPR-Cas9 and CRISPR-Cas12a in Combination With AAV6 Homology Donor Restores T Cell Function for XLP.Frontiers in genome editing · 2022Article
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Diacylglycerol kinase α inhibition cooperates with PD-1-targeted therapies to restore the T cell activation program.Cancer immunology, immunotherapy : CII · 2021Article
- Diacylglycerol Kinase alpha in X Linked Lymphoproliferative Disease Type 1.International journal of molecular sciences · 2021Review
- TIM-3 drives temporal differences in restimulation-induced cell death sensitivity in effector CD8Cell death & disease · 2021Article
- FOXP3 protects conventional human T cells from premature restimulation-induced cell death.Cellular & molecular immunology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
X-linked lymphoproliferative disease (XLP-1) is an often-fatal primary immunodeficiency associated with the exuberant expansion of activated CD8(+) T cells after Epstein-Barr virus (EBV) infection. XLP-1 is caused by defects in signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), an adaptor protein that modulates T cell receptor (TCR)-induced signaling. SAP-deficient T cells exhibit impaired TCR restimulation-induced cell death (RICD) and diminished TCR-induced inhibition of diacylglycerol kinase α (DGKα), leading to increased diacylglycerol metabolism and decreased signaling through Ras and PKCθ (protein kinase Cθ). We show that down-regulation of DGKα activity in SAP-deficient T cells restores diacylglycerol signaling at the immune synapse and rescues RICD via induction of the proapoptotic proteins NUR77 and NOR1. Pharmacological inhibition of DGKα prevents the excessive CD8(+) T cell expansion and interferon-γ production that occur in SAP-deficient mice after lymphocytic choriomeningitis virus infection without impairing lytic activity. Collectively, these data highlight DGKα as a viable therapeutic target to reverse the life-threatening EBV-associated immunopathology that occurs in XLP-1 patients.
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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.