PXD066533

PXD066533 is an original dataset announced via ProteomeXchange.

Title	Loss of Cullin 5 in myeloid cells protects against autoimmune neuroinflammation
Description	Autoimmune neuroinflammation occurs when an individual’s immune cells attack the brain, spinal cord or peripheral nerves. Several Suppressor of Cytokine Signaling (SOCS) proteins have been shown to limit pro-inflammatory signaling pathways in myeloid cells and prevent neuroinflammation. They rely on several mechanisms to accomplish this. Their SH2 domain allows them to bind phosphorylated tyrosine residues on surface receptors to prevent downstream signaling while their C-terminal SOCS domain can promote their assembly with Cullin5 (CUL5) to degrade signaling proteins. To date, the role of CUL5 in myeloid-cell-mediated function is poorly understood. Here we show that loss of Cul5 in myeloid cells resulted in reduced neuroinflammation and attenuated progression of Experimental Autoimmune Encephalomyelitis (EAE). Although peripheral CD4+ T cell activation was not overtly affected, Cul5-deficient macrophages in the Central Nervous System (CNS) demonstrated a significant shift towards an anti-inflammatory phenotype, characterized by increased expression of Arginase 1. This correlated with an enhanced frequency of FoxP3+ regulatory T cells. In contrast to what would be predicted if CUL5 and SOCS proteins work together to degrade pro-inflammatory cytokine signaling, Cul5 deletion in myeloid cells selectively enhanced IL-4-mediated Arginase 1 expression. These findings identify CUL5 as an unanticipated pro-inflammatory mediator during neuroinflammation and reveal its potential as a therapeutic target for autoimmune diseases.
HostingRepository	PRIDE
AnnounceDate	2025-08-04
AnnouncementXML	Submission_2025-08-04_11:58:05.221.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-24 07:29:13	ID requested
⏵ 1	2025-08-04 11:58:05	announced

Dataset with its publication pending

submitter keyword: T cell activation, CUL5, SH2 domain,Cytokine Signaling

Dr. Paula M Oliver
contact affiliation	Division of Protective Immunity Children’s Hospital of Philadelphia 816F ARC, 3615 Civic Center Boulevard Philadelphia, PA 19104
contact email	paulao@pennmedicine.upenn.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2025/08/PXD066533

PRIDE project URI

• PRIDE
  1. PXD066533
     1. Label: PRIDE project
     2. Name: Loss of Cullin 5 in myeloid cells protects against autoimmune neuroinflammation