PXD041654

PXD041654 is an original dataset announced via ProteomeXchange.

Title	GABA, glucose and insulin orchestrate CD4+ T cells effector functions
Description	Metabolic programs of immune cells are closely linked to their effector functions , where physiological molecules provide environmental cues and guidance. Exactly how it happens is still being unraveled. Insulin maintains normal blood glucose levels and glucose is themain source of energy and a precursor for many biomolecules in T cells, whereas γ-aminobutyric acid (GABA), best known as a neurotransmitter, is increasingly recognized as a regulatory molecule in the immune system. Here, we demonstrate that GABA-mediated reduction of metabolic activity and release of inflammatory molecules, including IFNγ and IL-10, was abolished in human CD4+ T cells, when the glucose concentration was elevated above normal levels. In a glucose concentration-dependent manner, insulin enhanced the GABAA receptors activated currents and GABA-dependent Ca2+ influx. GABA decreased, whereas insulin maintained glycolysis but in a SGLT (Na + -glucose transporter)-dependent manner, revealing expression of SGLTs in activated CD4+ T cells. The SGLTs antagonist phlorizin, alone or together with GABA, restored the inhibition of IFNγ and IL-10 release in presence of high glucose. This study exposes concerted effects of GABA, glucose and insulin on CD4+ T cells metabolic activity and release of inflammatory molecules, and identifies a role for SGLTs in CD4+ T cells function.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:22.372.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041654
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Erik Jansson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	amidated residue; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	MALDI Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-19 09:50:18	ID requested
1	2024-08-10 12:49:47	announced
⏵ 2	2024-10-22 06:54:23	announced	2024-10-22: Updated project metadata.

10.1016/j.ebiom.2024.105217;

Jin Z, Hammoud H, Bhandage AK, Korol SV, Trujeque-Ramos O, Koreli S, Gong Z, Chowdhury AI, Sandbaumh, ü, ter FA, Jansson ET, Lindsay RS, Christoffersson G, Andr, é, n PE, Carlsson PO, Bergsten P, Kamali-Moghaddam M, Birnir B, T cell functions is enhanced by insulin but impaired by high glucose levels. EBioMedicine, 105():105217(2024) [pubmed]

10.6019/PXD041654;

submitter keyword: CD4, GABA

Erik Jansson
contact affiliation	Department of Pharmaceutical Biosciences, Uppsala University
contact email	erik.jansson@farmbio.uu.se
lab head
Erik Jansson
contact affiliation	Uppsala University
contact email	erik.jansson@farmbio.uu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD041654

PRIDE project URI

• PRIDE
  1. PXD041654
     1. Label: PRIDE project
     2. Name: GABA, glucose and insulin orchestrate CD4+ T cells effector functions