Lymphocytic Choriomeningitis Virus Clone 13 Infection Results in CD8 T Cell-Mediated Host Mortality in Diacylglycerol Kinase α-Deficient Mice.

Diacylglycerol is a potent element of intracellular secondary signaling cascades whose production is enhanced by cell-surface receptor agonism and function is regulated by enzymatic degradation by diacylglycerol kinases (DGKs). In T cells, stringent regulation of the activity of this second messenger maintains an appropriate balance between effector function and anergy. In this article, we demonstrate that DGKα is an indispensable regulator of TCR-mediated activation of CD8 T cells in lymphocytic choriomeningitis virus Clone 13 viral infection. In the absence of DGKα, Clone 13 infection in a murine model results in a pathologic, proinflammatory state and a multicellular immunopathologic host death that is predominantly driven by CD8 effector T cells.

• Publication year

  2023

• Venue

  Journal of Immunology

• Publication date

  2023-03-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.4049/jimmunol.2101011PMID 36920384PMCID PMC10121876
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics

  2021cited by this paper
• DGK α and ζ Activities Control TH1 and TH17 Cell Differentiation

  2020cited by this paper
• Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling

  2020cited by this paper
• Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus

  2019cited by this paper
• AP-1 Transcription Factors as Regulators of Immune Responses in Cancer

  2019cited by this paper
• Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals

  2018cited by this paper
• Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics

  2018cited by this paper
• Myeloid-Derived Suppressor Cells Inhibit T Follicular Helper Cell Immune Response in Japanese Encephalitis Virus Infection

  2017cited by this paper
• Salmon: fast and bias-aware quantification of transcript expression using dual-phase inference

  2017cited by this paper
• The Reactome Pathway Knowledgebase

  2017cited by this paper
• Diacylglycerol Kinases in T Cell Tolerance and Effector Function

  2016cited by this paper
• IL-17+ CD8+ T cells: Differentiation, phenotype and role in inflammatory disease

  2016cited by this paper
• Diacylglycerol Kinases as Emerging Potential Drug Targets for a Variety of Diseases: An Update

  2016cited by this paper
• Redundant and specialized roles for diacylglycerol kinases α and ζ in the control of T cell functions

  2015cited by this paper
• Full-length RNA-seq from single cells using Smart-seq2

  2014cited by this paper
• Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

  2014cited by this paper
• Production and Differentiation of Myeloid Cells Driven by Proinflammatory Cytokines in Response to Acute Pneumovirus Infection in Mice

  2014cited by this paper
• Diacylglycerol kinase α establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse

  2014cited by this paper
• Diacylglycerol Kinase ζ Limits B Cell Antigen Receptor–Dependent Activation of ERK Signaling to Inhibit Early Antibody Responses

  2013cited by this paper
• Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity.

  2013cited by this paper
• Regulation of GPCR-mediated smooth muscle contraction: implications for asthma and pulmonary hypertension.

  2013cited by this paper
• Diacylglycerol Kinases: Regulated Controllers of T Cell Activation, Function, and Development

  2013cited by this paper
• Differential Regulation of Primary and Memory CD8 T Cell Immune Responses by Diacylglycerol Kinases

  2012cited by this paper
• clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters

  2012cited by this paper
• Cross-Disorder Analysis of Bipolar Risk Genes: Further Evidence of DGKH as a Risk Gene for Bipolar Disorder, but also Unipolar Depression and Adult ADHD

  2011cited by this paper
• SHP-1 in T Cells Limits the Production of CD8 Effector Cells without Impacting the Formation of Long-Lived Central Memory Cells

  2010cited by this paper
• Induction, function and regulation of IL‐17‐producing T cells

  2008cited by this paper
• Disruption of diacylglycerol metabolism impairs the induction of T cell anergy

  2006cited by this paper
• Enhanced T cell responses due to diacylglycerol kinase zeta deficiency.

  2003cited by this paper
• Role of Diacylglycerol Kinase α in the Attenuation of Receptor Signaling

  2001cited by this paper
• Gene Ontology: tool for the unification of biology

  2000cited by this paper
• Gene expression elicited by NFAT in the presence or absence of cooperative recruitment of Fos and Jun

  2000cited by this paper
• KEGG: Kyoto Encyclopedia of Genes and Genomes

  2000cited by this paper
• Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo

  1990cited by this paper

• Lpar5 regulates the CD8 T-cell response to persistent virus infection by altering exhaustion programming, survival, and NK receptor expression.

  2025cites this paper