PXD035964

PXD035964 is an original dataset announced via ProteomeXchange.

Title	NCF1-dependent low production of reactive oxygen species in plasmacytoid dendritic cells exacerbates lupus
Description	Low capacity to produce reactive oxygen species (ROS) due to mutations in neutrophil cytosolic factor 1 (NCF1/p47phox) is strongly associated with lupus development both in humans and mouse models. Here, we aim to identify the major mechanisms of the Ncf1-disease association. We found that plasmacytoid dendritic cells (pDCs), the most potent producers of type I IFNs, exacerbate pristane-induced lupus in ROS-defective Ncf1-mutant and human NCF1-339 variant carrying mice. ROS deficiency in mouse models with Ncf1 mutation or human NCF1-339 variant leads to enhanced pDC generation via the TLR7/AKT/mTOR pathway and accumulation at sites of inflammation, resulting in an increased IFNα secretion. The produced IFNα further stimulates the JAK1/STAT1 pathway, which we found is hyperreactive in ROS-deficient pDCs. This, in turn, leads to increased type I IFN signature and enhanced proinflammatory responses. Our discoveries explain the causative effect of dysfunctional Ncf1 and pathogenicity of pDCs in lupus.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:16.541.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amir Ata Saei
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-10 15:00:43	ID requested
1	2023-03-12 15:25:10	announced
⏵ 2	2023-11-14 08:44:18	announced	2023-11-14: Updated project metadata.

Luo H, Urbonaviciute V, Saei AA, Lyu H, Gaetani M, V, é, gv, á, ri Á, Li Y, Zubarev RA, Holmdahl R, NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions. JCI Insight, 8(7):(2023) [pubmed]

submitter keyword: Lupus, reactive oxygen species, plasmacytoid dendritic cells

Prof. Roman A.Zubarev
contact affiliation	Department of Medical Biochemistry and Biphysics, Karolinska Institute, Stockholm, Sweden
contact email	Roman.zubarev@ki.se
lab head
Amir Ata Saei
contact affiliation	Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	amirata.saei.dibavar@ki.se
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/2023/03/PXD035964

PRIDE project URI

• PRIDE
  1. PXD035964
     1. Label: PRIDE project
     2. Name: NCF1-dependent low production of reactive oxygen species in plasmacytoid dendritic cells exacerbates lupus