Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative proteomics of expanded resting and activated human MAIT (mucosal associated invariant T cells)

ABSTRACT: Mucosal associated invariant T (MAIT) cells are an abundant population of innate T cells that recognize bacterial ligands and play a key role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells undergo proliferative expansion and increase their production of effector molecules such as cytokines. In this study, we found that mRNA and protein the abundance of the key metabolism regulator and transcription factor MYC was increased in stimulated MAIT cells. Using quantitative mass spectrometry, we identified the activation of two MYC controlled metabolic pathways, amino acid transport and glycolysis, both of which were necessary for MAIT cell proliferation. Finally, we showed that MAIT cells isolated from people with obesity showed decreased MYC mRNA abundance upon activation, which was associated with defective MAIT cell proliferation and functional responses. Collectively, our data uncovers the importance of MYC-regulated metabolism for MAIT cell proliferation and provides additional insight into the molecular basis for the functional defects of MAIT cells in obesity.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Blood

SUBMITTER: Andrew Howden

LAB HEAD: Dr Andrew Hogan

PROVIDER: PXD041544 | Pride | 2023-04-20

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Doxycycline treated cytotoxic T lymphocytes

Project description:Recent work in immunometabolism has emphasised the role of mitochondria in both the innate and adaptive immune system. Mitochondria are important in T cell development and differentiation, but less is known about their role in CD8+ effector T cells (CTLs). We found that CTLs that lack the mitochondrial deubiquitinase USP30 undergo promiscuous mitophagy, destroying most of the cellular mitochondria. Surprisingly, this results in a markedly diminished killing capacity, while motility, signalling and secretion remain intact. This study uses quantitative DIA proteomics to measure the impact of USP30 deficiency on the global proteome of IL-2 maintained, 4.5 h TCR retriggered and 4.5 h TCR retriggered + cycloheximide CTL. We also measured the impact of pharmacologically inhibiting mitochondrial translation by performing Quantitative DIA proteomics on IL2 maintained or TCR retriggered CTL treated with the mitochondrial translation inhibitor doxycycline for 4.5 hrs. Unexpectedly, inhibition of mitochondrial translation, through genetic or pharmacologic methods, was the mechanism by which CTL killing was impaired. Reduced mitochondrial translation triggered attenuated cytosolic translation which precluded replenishment of secreted effector molecules thereby limiting the capacity of CTLs to serially kill multiple targets. Thus, mitochondria emerge as a previously unappreciated homeostatic regulator of protein translation required for serial CTL killing.

2022-06-09 | PXD026948 | Pride

Gene expression profiles of MAIT cells, MAIT-iPSCs, hiPSCs, hESCs, and reMAIT cells

Project description:To show the similarity among MAIT-iPSCs, hiPSCs and hESCs and the gradual change of global gene expression of reMAIT cells along with differentiation, this experiment was designed. MAIT cells, MAIT-iPSCs, hiPSCs, hESCs, MAIT cells, and reMAIT cells at the several differerent stages of differentiation were collected. Then, they were applied in this experiment.

2013-03-21 | E-GEOD-44559 | biostudies-arrayexpress

A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS

Project description:Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus induced disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with SARS-CoV-2. We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism to promote glutamine utilisation, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population it does not impact upon prothrombotic hyperinflammatory neutrophil signatures.

2021-02-03 | PXD023834 | Pride

Proteomics of Day 6 IL-2 or IL-15 expanded wild-type and Pim1/Pim2 double knockout CD8+ T cells.

Project description:T cell antigen-receptor (TCR) and cytokine receptor engagement trigger large changes in Serine/Threonine kinase signalling networks to drive T cell activation and differentiation. The role of only few kinase signalling pathways have been studied in detail, and in this context, Pim kinases are an interesting, yet understudied, family of Serine/Threonine kinases, with reported roles in key processes including survival, proliferation, metabolism across a range of cell types. T lymphocytes predominantly express PIM1 and PIM2, which are rapidly induced by TCR, costimulation and cytokine signalling. Using high-resolution mass spectrometry and RNAseq we systematically examine the impact of Pim1/Pim2 double deficiency on in vitro differentiated cytotoxic T lymphocytes (CTL) expanded in the cytokines IL-2 and IL-15 to generate effector or memory T cells respectively. We find that Pim kinases are dispensable for IL-15-driven memory cell differentiation, but that Pim1/2-deficiency has a selective impact on the transcriptome and proteome of IL-2 driven effector CD8 T cells. ~75% of Pim kinase-regulated proteins were not predicted by differences in mRNA in IL-2 expanded CTL. These included proteins that are key for effector cell function: glucose transporters SLC2A1 and SLC2A3 and key effector molecules Granzyme A and B. We find that Pim kinases have this effect via control of protein translation. Another key finding was that the mRNA for key T cell homing receptors Ccr7, S1pr1 and CD62L was increased in Pim1/2-deficienct T cells and that this functionally enhancing homing to secondary lymphoid organs.

2024-04-15 | PXD051213 | Pride

RNA helicase EIF4A1-mediated translation is essential for the GC response

Project description:EIF4A1 and cofactors EIF4B and EIF4H have been well characterised in cancers, including B cell malignancies, for their ability to promote the translation of oncogenes with structured 5’ untranslated regions. However, very little is known of their roles in non-malignant cells. Using mouse models to delete Eif4a1, Eif4b or Eif4h in B cells we show that EIF4A1, but not EIF4B or EIF4H, is essential for B cell development and the germinal centre response. Following B cell activation in vitro, EIF4A1 facilitates an increased rate of protein synthesis, MYC expression and expression of cell cycle regulators. However, EIF4A1-deficient cells remain viable whereas inhibition of EIF4A1 and EIF4A2 by Hippuristanol treatment induces cell death.

2023-11-09 | PXD046710 | Pride

Effect of LPS and the glucocorticoid dexamethasone on the mouse Bone Marrow Derived Macrophage Proteome

Project description:The concentrations and copy number of proteins in the mouse Bone Marrow Derived proteome was determined for control, 10 ng/mL LPS stimulation, and LPS stimulation plus the addition of 100 nM dexamethasone, after an incubation for 24 hours and with four biological replicates for each condition. Over 6000 proteins were detected, 410 of which were upregulated by LPS (> 1.5-fold increase, adjusted p value < 0.05). 125 of these LPS-induced proteins were significantly regulated by Dexamethason > 1.5 fold 899 increase or decrease, adjusted p value <0.05).

2024-01-26 | PXD041375 | Pride

Quantitative proteomics reveals tissue-specific, infection-induced and species-specific neutrophil protein signatures – human blood neutrophils

Project description:Neutrophils are one of the first responders to infection and are a key component of the innate immune system through their ability to phagocytose and kill invading pathogens, secrete antimicrobial molecules and produce extracellular traps. Neutrophils are produced in the bone marrow, circulate within the blood and upon immune challenge migrate to the site of infection. We wanted to understand whether this transition shapes the mouse neutrophil protein landscape, how the mouse neutrophil proteome is impacted by systemic infection and perform a comparative analysis of human and mouse neutrophils. Using quantitative mass spectrometry we reveal tissue-specific, infection-induced and species-specific neutrophil protein signatures. We show a high degree of proteomic conservation between mouse bone marrow, blood and peritoneal neutrophils, but also identify key differences in the molecules that these cells express for sensing and responding to their environment. Systemic infection triggers a change in the bone marrow neutrophil population with considerable impact on the core machinery for protein synthesis and DNA replication along with environmental sensors. We also reveal profound differences in mouse and human blood neutrophils, particularly their granule contents and their receptor repertoires. Our proteomics data provides a valuable resource for understanding neutrophil function and phenotypes across species and model systems.

2024-03-13 | PXD044569 | Pride

Quantitative proteomics reveals tissue-specific, infection-induced and species-specific neutrophil protein signatures – mouse bone marrow, blood and peritoneal cavity neutrophils

2024-03-13 | PXD044568 | Pride

Mass Spectrometry identifies temporal changes and hallmarks of Delayed Recovery in the COVID19 Neutrophil proteomes

Project description:High-resolution mass spectrometry and the parallel quantitative evaluation of thousands of proteins has been used to characterise the proteomes of peripheral blood neutrophils from >200 individuals. This work has comprehensively mapped neutrophil molecular changes associated with mild versus severe COVID19 and identified significant quantitative changes in more than 1700 proteins in neutrophils from patients hospitalised with COVID19 versus patients with non-COVID19 acute respiratory infections. The study identifies neutrophil protein signatures associated with COVID19 disease severity. The data also show that alterations in neutrophil proteomes can persist in fully recovered patients and identify distinct neutrophil proteomes in recovered versus non recovered patients. Our study provides novel insights into neutrophil responses during acute COVID-19 and reveal that altered neutrophil phenotypes persist in convalescent COVID19 infections.

2022-08-17 | PXD036082 | Pride

Mass Spectrometry identifies temporal changes and hallmarks of Delayed Recovery in the COVID19 Neutrophil proteomes part2

Project description:Mass Spectrometry identifies temporal changes and hallmarks of Delayed Recovery in the COVID19 Neutrophil proteomes MTD project_description High-resolution mass spectrometry and the parallel quantitative evaluation of thousands of proteins has been used to characterise the proteomes of peripheral blood neutrophils from >200 individuals. This work has comprehensively mapped neutrophil molecular changes associated with mild versus severe COVID19 and identified significant quantitative changes in more than 1700 proteins in neutrophils from patients hospitalised with COVID19 versus patients with non-COVID19 acute respiratory infections. The study identifies neutrophil protein signatures associated with COVID19 disease severity. The data also show that alterations in neutrophil proteomes can persist in fully recovered patients and identify distinct neutrophil proteomes in recovered versus non recovered patients. Our study provides novel insights into neutrophil responses during acute COVID-19 and reveal that altered neutrophil phenotypes persist in convalescent COVID19 infections.

2022-08-17 | PXD036089 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data