PXD037754-1

PXD037754 is an original dataset announced via ProteomeXchange.

Title	P2X7 signaling drives Th1 cell differentiation through metabolic reprogramming for aerobic glycolysis
Description	This study provides evidence on the molecular mechanisms by which P2RX7 signaling promotes Th1 cell differentiation. P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-polarized CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, ATP synthase blockade in vitro and the consequent inhibition of oxidative phosphorylation, which forces cells to use aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7. These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 cell differentiation and suggest that ATP synthase inhibition is a fundamental mechanism by which P2X7 signaling induces the Th1 response.
HostingRepository	PRIDE
AnnounceDate	2023-03-08
AnnouncementXML	Submission_2023-03-08_08:28:08.543.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	VeronicaSantiago
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-27 02:36:12	ID requested
⏵ 1	2023-03-08 08:28:08	announced
2	2023-11-14 08:59:45	announced	2023-11-14: Updated project metadata.

submitter keyword: aerobic glycolysis, malaria,P2X7 signaling, Th1 cell differentiation

Maria Regina D’ImpérioLima
contact affiliation	- Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
contact email	relima@usp.br
lab head
VeronicaSantiago
contact affiliation	University of Sao Paulo
contact email	veronicafeijoli@usp.br
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037754
     1. Label: PRIDE project
     2. Name: P2X7 signaling drives Th1 cell differentiation through metabolic reprogramming for aerobic glycolysis