PXD037723

PXD037723 is an original dataset announced via ProteomeXchange.

Title	Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation
Description	Alcohol is among the most widely consumed dietary substances. While excessive alcohol consumption damages the liver, heart and brain, clinical observations also suggest that alcohol has strong immunoregulatory properties. However, little is known about the mechanistic effects of alcohol on the immune system. T cell functions such as migration, immune synapse formation and activation depend on the reorganization of the cytoskeleton. In this study, we show that acetate, the metabolite of alcohol, effectively inhibits the migratory capacity of T cells through increased tissue acetate levels that lead to acetylation of cortactin, a protein that binds filamentous actin and facilitates branching. Current knowledge of cortactin’s role in T cells is limited. Here we demonstrate and confirm that primary mouse and human T cells express cortactin and acetylation of cortactin inhibits actin filament binding leading to reduced filament branching, lamellipodia formation and T cell migration. Mutated acetylation-resistant cortactin rescued the acetate-induced inhibition of T cell migration. Primary mouse cortactin knock-out T cells exhibited severely reduced T cell migration. Furthermore, acetate-induced cytoskeletal changes effectively inhibited activation, proliferation, and immune synapse formation in T cells exposed to acetate at tissue concentrations reached by alcohol consumption. In summary, these data show that acetate, the key metabolite of alcohol, is inhibiting T cell mediated immune responses by modulating the biomechanics of T cells through their cytoskeletal function.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:09:50.008.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joerg Hofmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-26 00:59:49	ID requested
1	2023-10-24 12:18:36	announced
2	2023-11-14 09:09:39	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:09:50	announced	2024-10-22: Updated project metadata.

Azizov V, H, ü, bner M, Frech M, Hofmann J, Kubankova M, Lapuente D, Tenbusch M, Guck J, Schett G, Zaiss MM, cell function by promoting cortactin acetylation. iScience, 26(7):107230(2023) [pubmed]

10.1016/j.isci.2023.107230;

submitter keyword: cytoskeleton, acetate, filamentous actin,Alcohol, cell trafficking, cell biomechanics

Prof. Dr. Mario Zaiss
contact affiliation	1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander- University Erlangen-Nürnberg and Universitätsklinikum Erlangen; Erlangen, Germany
contact email	mario.zaiss@fau.de
lab head
Joerg Hofmann
contact affiliation	FAU Erlangen-Nürnberg
contact email	joerg.hofmann@fau.de
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/2023/10/PXD037723

PRIDE project URI

• PRIDE
  1. PXD037723
     1. Label: PRIDE project
     2. Name: Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation