PXD052113-1

PXD052113 is an original dataset announced via ProteomeXchange.

Title	Platelet-derived transcription factors license human monocyte inflammation
Description	CD14+ monocytes, the predominant population in human blood, are primarily engaged in host defense and pro-inflammatory cytokine responses. Aberrant monocyte activity causes life-threatening cytokine storms, while dysfunctional monocytes lead to 'immunoparalysis.' Understanding the mechanisms controlling monocyte functions is therefore paramount. Here, we reveal platelets' vital role in human monocytes' pro-inflammatory responses. Natural low platelet counts in patients with immune thrombocytopenia (ITP) , platelet depletion in healthy human monocytes, or in vivo platelet depletion in mice, result in monocyte immunoparalysis, characterized by reduced pro-inflammatory gene expression and weakened cytokine responses to immune challenge. Remarkably, supplementation with fresh platelets reverses monocyte immunoparalysis. In mice, thrombocytopenia results in down-regulation of myeloid innate immune genes, and compromised host defense transcriptional programs in monocytes despite normal responses to LPS. Platelets control monocyte cytokines independently of traditional cross-talk pathways, acting as reservoirs of transcription factors like NF?B and MAPK p38. We pinpointed a vesicle-derived NF?B2 transfer to human monocytes by mass spectrometry-based proteomics. Functionally, platelets proportionally restored impaired cytokine secretion in human monocytes lacking MAPK p38a and NF?B p65 and NF?B2. We unveil the intercellular transfer of inflammatory regulators, positioning platelets as central checkpoints in monocyte-mediated inflammation.
HostingRepository	PRIDE
AnnounceDate	2024-08-14
AnnouncementXML	Submission_2024-08-14_02:40:38.786.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sebastian Kallabis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-08 08:02:12	ID requested
⏵ 1	2024-08-14 02:40:39	announced
2	2024-10-22 06:54:58	announced	2024-10-22: Updated project metadata.

10.1038/S44321-024-00093-3;

submitter keyword: Immune Thrombocytopenia,Cytokines, Toll-like Receptors, Inflammasomes, Immunoparalysis

Bernardo S. Franklin
contact affiliation	Institute of Innate Immunity, University Hospitals, Medical Faculty, University of Bonn, Bonn, Germany
contact email	franklin@uni-bonn.de
lab head
Sebastian Kallabis
contact affiliation	Department for Systems Immunology & Proteomics Institute of Innate Immunity University Hospital Bonn Venusberg - Campus 1 53127 Bonn Germany
contact email	kallabis@uni-bonn.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/2024/08/PXD052113

PRIDE project URI

• PRIDE
  1. PXD052113
     1. Label: PRIDE project
     2. Name: Platelet-derived transcription factors license human monocyte inflammation