PXD062260

PXD062260 is an original dataset announced via ProteomeXchange.

Title	ALS-associated TDP-43 aggregates drive innate and adaptive immune cell activation
Description	Amyotrophic lateral sclerosis is the most common and fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology of the master RNA regulator, Transactive Response DNA Binding protein (TDP-43). Despite the prevalence TDP-43 pathology in ALS motor neurons, recent findings suggest immune dysfunction is a determinant of disease progression in patients. Whether TDP-43 aggregates elicit immune responses remains underexplored. In this study, we demonstrate that TDP-43 aggregates are internalized by antigen presenting cell populations, cause vesicle rupture, and drive innate and adaptive immune cell activation by way of antigen presentation. Using a multiplex imaging platform, we observed enrichment of activated microglia/macrophages in ALS white matter that correlated with phosphorylated TDP-43 accumulation, CD8 T-cell infiltration, and major histocompatibility complex expression. Taken together, this study sheds light on a novel cellular response to TDP43 aggregates through an immunological lens.
HostingRepository	PRIDE
AnnounceDate	2025-04-08
AnnouncementXML	Submission_2025-04-08_09:03:37.946.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Xie
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-26 06:25:20	ID requested
⏵ 1	2025-04-08 09:03:38	announced

Dataset with its publication pending

submitter keyword: TDP-43,ALS

Todd J. Cohen
contact affiliation	Department of Neurology, University of North Carolina, Chapel Hill, NC, USA
contact email	toddcohen@neurology.unc.edu
lab head
Ling Xie
contact affiliation	UNC at Chapel Hill
contact email	xiel@email.unc.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/2025/04/PXD062260

PRIDE project URI

• PRIDE
  1. PXD062260
     1. Label: PRIDE project
     2. Name: ALS-associated TDP-43 aggregates drive innate and adaptive immune cell activation