PXD066223-1

PXD066223 is an original dataset announced via ProteomeXchange.

Title	TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets
Description	Dendritic cells (DCs) rely on Toll-like receptor 9 (TLR9) to detect unmethylated CpG motifs in microbial DNA, triggering essential immune responses. While the downstream signaling pathways of TLR9 activation are well characterized, their impact on S-palmitoylation is unknown. S-palmitoylation, involving the reversible attachment of palmitic acid to cysteine residues, plays a crucial role in regulating protein function and is catalyzed by the ZDHHC family of palmitoyl-acyltransferases (PATs). In this study, we investigated the S-palmitoylated proteome of bone marrow-derived GM-CSF DCs (GM-DCs) at resting and following TLR9 activation with CpGB. Using the click-chemistry compatible analog 17-octadecynoic acid (17-ODYA) and mass spectrometry-(MS)-based proteomics, we characterized dynamic remodeling of S-palmitoylation in response to TLR9 activation. This included enrichment of targets involved in immune and metabolic pathways. Transcriptomic analysis of mice and human DCs revealed TLR9-driven modulation of ZDHHC genes. Subsequently, we explored the contribution of ZDHHC9 to the regulation of S-palmitoylation in DCs. We found that Zdhhc9 deficiency affects the S-palmitoylation of specific proteins, revealing potential ZDHHC9 substrates. Interestingly, modulation of Zdhhc9 expression alone did not influence DC maturation, suggesting that other PATs might compensate for its activity. Together, our findings reveal a novel layer of regulation in TLR9 signaling mediated by S-palmitoylation.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_18:55:50.420.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JUAN NAHUEL QUIROZ
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	palmitoylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 10:14:12	ID requested
⏵ 1	2025-08-24 18:55:51	announced

10.1002/eji.70039;

Quiroz JN, Sielaff M, Kondrateva D, Boukhallouk F, Godoy GJ, Molina CR, Moonen B, Motran CC, Bogie J, Luj, á, n HD, Tenzer S, Sparwasser T, Berod L, TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets. Eur J Immunol, 55(8):e70039(2025) [pubmed]

submitter keyword: TLR9, Dendritic cells., S-palmitoylation

Luciana Berod
contact affiliation	Institute of Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, 55131, Germany Research Center for Immunotherapy (FZI), University Medical Center Mainz, 55131 Mainz, Germany.
contact email	berod@uni-mainz.de
lab head
JUAN NAHUEL QUIROZ
contact affiliation	Institut für Molekulare Medizin
contact email	juan.nahuelq@gmail.com
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/2025/08/PXD066223

PRIDE project URI

• PRIDE
  1. PXD066223
     1. Label: PRIDE project
     2. Name: TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets