Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SCD2-mediated monounsaturated fatty acid metabolism regulates cGAS-STING-dependent type I IFN in mouse CD4+ T cells

ABSTRACT: ACC1 is known to rate limitng enzyme of fatty acid biosynthesis. We report that modulation of fatty acid biosynthesis pathway increased tonic expression of anti-viral genes. RNA sequence was conducted to compare global gene expression between control, ACC1 inhibitor (TOFA)-treated, ACC1 KO and IFNb-treated Th1 cells. We found that inhibition or deletion of ACC1 resulted in the enhancement of anti-viral genes expression as comparable level to IFNb-treated Th1 cells. This study provides a framework for the relationship between fatty acid biosynthesis pathway and anti-viral responses in CD4 T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE173728 | GEO | 2021/05/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Acc1 determines memory potential of individual CD4+ T cells by regulating de novo fatty acid biosynthesis [RT-PCR]

Project description:Immunological memory is central to adaptive immunity and protection from disease. Changing metabolic demands as antigen-specific T cells transition from effector to memory have been well documented, but the cell-specific pathways and molecules that govern this transition are poorly defined. ACC1 is a rate-limiting enzym in fatty acid biosynthesis. We show that genetic deletion of ACC1 enhanced the formation of CD4+ T cell memory, and that inhibition of ACC1 function enhanced memory T cell formation during parasite infection in mice. ACC1-deficient effector Th cells had similar metabolic signatures to wild-type memory Th cells, and Acaca expression was inversely correlated with a memory gene signature in individual cells. Single cell analysis allowed us to identify a memory precursor-enriched population (CCR7hiCD137lo) present during early differentiation of effector CD4+ T cells. Thus, fatty acid metabolism directs cell fate determination during the generation of memory CD4+ T cells.

2018-11-30 | GSE122862 | GEO

Acc1 determines memory potential of individual CD4+ T cells by regulating de novo fatty acid biosynthesis [microarray]

2018-11-30 | GSE122861 | GEO

Acc1 determines memory potential of individual CD4+ T cells by regulating de novo fatty acid biosynthesis [RNA-seq]

2018-11-30 | GSE120667 | GEO

De novo fatty acid synthesis in invariant NKT cells is critical for the development of airway hyperresponsiveness

Project description:Allergic responses in airway against house dust mites (HDMs) depend on lipid metabolism. However, whether the state of lipid metabolism in iNKT cells serves as a critical mechanism to impact development of allergic asthma remains elusive. Here, we showed that acetyl-CoA-Carboxylase 1 (ACC1), a key enzyme for fatty acid synthesis, was highly expressed in iNKT cells from asthmatic lungs. In ovalbumin (OVA)- and HDM-induced allergic asthma models, Cd4-CreAcc1fl/fl mice exhibited impaired homeostasis of iNKT cells and failed to develop AHR. ACC1-deficient iNKT cells reduced intracellular lipid concentration and expression of fatty acid binding proteins (FABPs) and peroxisome proliferator-activated receptor-gamma (PPAR-γ), whereas these cells were increased in glycolytic capacity. Moreover, ACC1-FABP-PPAR-γ axis regulated cell death of ACC1-deficient iNKT cells. Adoptive transfer of wild type (WT) iNKT cells restored AHR in Jɑ18 knockout mice in OVA or HDM-induced asthma models, whereas that of ACC1-deficient iNKT cells did not, indicating that fatty acid synthesis in iNKT cells is one of main contributors to the development of AHR. Our finding demonstrate fatty acid metabolism in iNKT cells is critical contributor for the development of AHR and airway inflammation in asthma.

2022-06-15 | GSE205761 | GEO

Malonylation of Acetyl-CoA Carboxylase 1 Promotes Hepatic Steatosis and Is Attenuated by Ketogenic Diet in NAFLD

Project description:Protein post-translational modifications (PTMs) participate in important bioactive regulatory processes and therefore can help elucidate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the involvement of PTMs in ketogenic diet (KD)-improved fatty liver by multi-omics and reveal a core target of lysine malonylation, acetyl-CoA carboxylase 1 (ACC1). ACC1 protein levels and Lys1523 malonylation are significantly decreased by KD. It is discovered that a malonylation-mimic mutant in ACC1 increases its enzyme activity and stability to promote hepatic steatosis, whereas the malonylation-null mutant upregulates the ubiquitination degradation of ACC1. A customized Lys1523ACC1 malonylation antibody confirms the increased malonylation of ACC1 in the NAFLD samples. Overall, the lysine malonylation of ACC1 is attenuated by KD in NAFLD and plays an important role in promoting hepatic steatosis. Malonylation is critical for ACC1 activity and stability, highlighting the anti-malonylation effect of ACC1 as a potential strategy for treating NAFLD.

2023-07-21 | PXD040481 | Pride

XB001: Shortening of membrane lipid acyl chains compensates for phosphatidylcholine deficiency in choline‐auxotroph yeast

Project description:Phosphatidylcholine (PC) is an abundant membrane lipid component in most eukaryotes including yeast. PC has been assigned a multitude of functions in addition to that of building block of the lipid bilayer. Here we show that PC is evolvable essential in yeast by isolating suppressor mutants devoid of PC that exhibit robust growth. The requirement for PC is suppressed by monosomy of chromosome XV, or by a point mutation in the ACC1 gene encoding acetyl-CoA carboxylase. Although these two genetic adaptations rewire lipid biosynthesis differently, both decrease Acc1 activity thereby reducing the average acyl chain length. Accordingly, soraphen A, a specific inhibitor of Acc1, rescues a yeast mutant with deficient PC synthesis. In the aneuploid suppressor, up-regulation of lipid synthesis is instrumental to accomplish feed-back inhibition of Acc1 by acyl-CoA produced by the fatty acid synthase (FAS). The results show that yeast regulates acyl chain length by fine-tuning the activities of Acc1 and FAS, and indicate that PC evolved by benefitting the maintenance of membrane fluidity.

2021-08-04 | GSE75725 | GEO

Malonylation of Acetyl-CoA Carboxylase 1 Promotes Hepatic Steatosis and Is Attenuated by Ketogenic Diet in NAFLD

2023-03-05 | GSE226139 | GEO

ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation

Project description:T cells possess distinguishing effector functions and drive inflammatory disorders. We have previously identified IL-5-producing Th2 cells as the pathogenic population predominantly involved in the pathology of allergic inflammation. However, the cell-intrinsic signaling pathways that control the pathogenic Th2 cell function are still unclear. We herein report the high expression of acetyl-CoA carboxylase 1 (ACC1) in pathogenic CD4+ T cell population in the lung and skin. The genetic deletion of CD4+ T cell-intrinsic ACC1 dampened eosinophilic and basophilic inflammation in the lung and skin by constraining IL-5 or IL-3 production. Mechanistically, ACC1-dependent fatty acid biosynthesis induces the pathogenic cytokine production of CD4+ T cells via metabolic reprogramming and the availability of acetyl-CoA for epigenetic regulation. We thus identified a distinct phenotype of the pathogenic T cell population in the lung and skin, and ACC1 was shown to be an essential regulator controlling the pathogenic function of these populations to promote type 2 inflammation.

2021-10-12 | GSE185743 | GEO