PXD048462

PXD048462 is an original dataset announced via ProteomeXchange.

Title	CD4 T cell contact drives macrophage cell cycle progression and susceptibility to lentiviral transduction
Description	Macrophages are typically quiescent cells residing in G0, though tissue macrophages have been shown to proliferate locally in tissues; we previously demonstrated that differentiated monocyte derived macrophages (MDM) can be stimulated to re-enter G1 phase of the cell cycle from G0, without cell division. Entry into G1 correlates with an increase in CDK1 expression which phosphorylates the deoxynucleotide-triphosphate hydrolase SAMHD1 at position 592. SAMHD1 not only regulates cellular dNTP levels, but is also a restriction factor for virus replication of HIV-1 and DNA viruses. Here we show that contact with autologous CD4 T cells leads to antigen-independent macrophage cell cycle progression from G0-G1, accompanied by expression of cell cycle associated proteins, including CDK1, and the activation of the canonical MEK-ERK pathway. Further, macrophage cell cycle progression can be blocked not only by anti-cancer drugs targeting the MEK-ERK axis such as Palcociclib, but also by pre-treatment with EGFR antibody, providing additional evidence for cell surface interactions driving proliferative responses. Cell contact with uninfected CD4 T cells renders macrophages ten-fold more susceptible to transduction with VSV-G pseudotyped HIV-1 particles. These findings have important implications for HIV reservoirs in macrophages and potential targeting of macrophages for gene therapy.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:38:07.096.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD048462
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-11 07:04:40	ID requested
⏵ 1	2025-05-06 12:38:07	announced

10.1038/s41392-024-02053-2;

10.6019/PXD048462;

Mlcochova P, Zhao N, Shabana O, Fischer R, Gupta RK, CD4 T cell contact drives macrophage cell cycle G0-G1 transition. Signal Transduct Target Ther, 9(1):348(2024) [pubmed]

submitter keyword: macrophage, cell cycle

Roman Fischer
contact affiliation	University of Oxford Discovery Proteomics (DisPro)
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048462
     1. Label: PRIDE project
     2. Name: CD4 T cell contact drives macrophage cell cycle progression and susceptibility to lentiviral transduction