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PXD052113

PXD052113 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePlatelet-derived transcription factors license human monocyte inflammation
DescriptionCD14+ 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:54:58.022.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSebastian Kallabis
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-05-08 08:02:12ID requested
12024-08-14 02:40:39announced
22024-10-22 06:54:58announced2024-10-22: Updated project metadata.
Publication List
10.1038/S44321-024-00093-3;
Keyword List
submitter keyword: Immune Thrombocytopenia,Cytokines, Toll-like Receptors, Inflammasomes, Immunoparalysis
Contact List
Bernardo S. Franklin
contact affiliationInstitute of Innate Immunity, University Hospitals, Medical Faculty, University of Bonn, Bonn, Germany
contact emailfranklin@uni-bonn.de
lab head
Sebastian Kallabis
contact affiliationDepartment for Systems Immunology & Proteomics Institute of Innate Immunity University Hospital Bonn Venusberg - Campus 1 53127 Bonn Germany
contact emailkallabis@uni-bonn.de
dataset submitter
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Dataset FTP location
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