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Publication

Tricarboxylic Acid Cycle Activity and Remodeling of Glycerophosphocholine Lipids Support Cytokine Induction in Response to Fungal Patterns.

Cell reports | 2019

Increased glycolysis parallels immune cell activation, but the role of pyruvate remains largely unexplored. We found that stimulation of dendritic cells with the fungal surrogate zymosan causes decreases of pyruvate, citrate, itaconate, and α-ketoglutarate, while increasing oxaloacetate, succinate, lactate, oxygen consumption, and pyruvate dehydrogenase activity. Expression of IL10 and IL23A (the gene encoding the p19 chain of IL-23) depended on pyruvate dehydrogenase activity. Mechanistically, pyruvate reinforced histone H3 acetylation, and acetate rescued the effect of mitochondrial pyruvate carrier inhibition, most likely because it is a substrate of the acetyl-CoA producing enzyme ACSS2. Mice lacking the receptor of the lipid mediator platelet-activating factor (PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) showed reduced production of IL-10 and IL-23 that is explained by the requirement of acetyl-CoA for PAF biosynthesis and its ensuing autocrine function. Acetyl-CoA therefore intertwines fatty acid remodeling of glycerophospholipids and energetic metabolism during cytokine induction.

Pubmed ID: 30970255 RIS Download

Research resources used in this publication

Phospho-Stat-3 (tyr705) (RRID:AB_331586) (antibody)

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

None

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This is a list of tools and resources that we have found mentioned in this publication.

PRISM (tool)

RRID:SCR_005375

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.

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PeproTech (tool)

RRID:SCR_006802

An Antibody supplier

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Adobe Photoshop (tool)

RRID:SCR_014199

Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.

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Kaluza (tool)

RRID:SCR_016182

Flow cytometry analysis software.

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AceCS1 (D19C6) XP(tm) Rabbit mAb (antibody)

RRID:AB_2222710

This monoclonal targets Acss2

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Phospho-Stat-3 (tyr705) (antibody)

RRID:AB_331586

This polyclonal targets Phospho-Stat3 (Tyr705) Antibody detects endogenous levels of Stat3 only when phosphorylated at Tyr705. The antibody does not cross-react with other Stat proteins when phosphorylated on the corresponding tyrosine residue. Does cross-react withPhospho-EGFR

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