PXD035964 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: Lupus, reactive oxygen species, plasmacytoid dendritic cells |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035964
- Label: PRIDE project
- Name: NCF1-dependent low production of reactive oxygen species in plasmacytoid dendritic cells exacerbates lupus