PXD058775-1

PXD058775 is an original dataset announced via ProteomeXchange.

Title	DNA Damage in Macrophages Drives Immune Autoreactivity via Nuclear Antigen Presentation
Description	Aging and DNA damage increase the risk of chronic inflammation and autoimmunity, yet their molecular underpinnings remain unclear. Here, we uncover a DNA damage-driven mechanism in macrophages that triggers immune autoreactivity. Using Er1Lyz2/- animals with a macrophage-specific DNA repair defect in ERCC1-XPF, we demonstrate that monocyte-derived macrophages with persistent DNA damage activate the immune system, drive polyclonal T-cell responses, and generate anti-nuclear autoantibodies. Proteomic and immunopeptidomic analyses reveal a distinct MHC-II antigen repertoire in these macrophages, enriched in nuclear and ribosomal peptides, relying on autophagy for nuclear cargo delivery to MHC-II. Aged macrophages exhibit a similar lysosomal cargo profile, linking autophagy-driven nuclear antigen presentation to immune activation. Notably, inhibiting autophagy in Er1Lyz2/⁻ mice suppresses autoimmune features, pinpointing autophagy-facilitated nuclear antigen processing as a central driver of age-related autoimmunity. These findings establish DNA damage-induced autophagy in macrophages as a pivotal mechanism linking aging to autoimmunity, and unveiling potential targets for interventions to mitigate age-related immune dysregulation.
HostingRepository	PRIDE
AnnounceDate	2025-12-02
AnnouncementXML	Submission_2025-12-02_13:01:07.549.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	George Garinis
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-11 07:30:10	ID requested
⏵ 1	2025-12-02 13:01:08	announced

Dataset with its publication pending

submitter keyword: DNA damage

immunosenescence

antigen presentation

autophagy

immunopeptidomics

autoimmune responses

T-cell responses

George A. Garinis
contact affiliation	Department of Biology, University of Crete, Heraklion, Crete, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, GR70013, Heraklion, Crete, Greece
contact email	garinis@imbb.forth.gr
lab head
George Garinis
contact affiliation	University of Crete - IMBB, FoRTH
contact email	garinis@imbb.forth.gr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058775
     1. Label: PRIDE project
     2. Name: DNA Damage in Macrophages Drives Immune Autoreactivity via Nuclear Antigen Presentation