PXD052113 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Keyword List
submitter keyword: Immune Thrombocytopenia,Cytokines, Toll-like Receptors, Inflammasomes, Immunoparalysis |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052113
- Label: PRIDE project
- Name: Platelet-derived transcription factors license human monocyte inflammation