PXD034102

PXD034102 is an original dataset announced via ProteomeXchange.

Title	Aberrant expression of transglutaminase 2 in pancreas and thymus of NOD mice underscores the importance of deamidation in neoantigen generation.
Description	Post-translational modifications can lead to a break in immune tolerance in autoimmune diseases such as type 1 diabetes (T1D). Deamidation, the conversion of glutamine to glutamic acid by transglutaminase (TGM) enzymes, is a post-translational modification of interest, with deamidated peptides being reported as autoantigens in T1D. However, little is known about how Tgm2, the most ubiquitously expressed Tgm isoform, is regulated and how tolerance against deamidated peptides is lost. Here, we report on the aberrant expression and regulation of Tgm2, in the pancreas and thymus of NOD mice. We demonstrate that Tgm2 expression is induced by the inflammatory cytokines IL1β and IFNγ in a synergistic manner and that murine pancreatic islets of NOD mice have higher Tgm2 levels, while Tgm2 levels in thymic mTECs are reduced. We thus provide the first direct evidence to our knowledge that central tolerance establishment against deamidated peptides might be impaired due to lower Tgm2 expression in NOD mice, which together with the aberrantly high levels of deamidated peptides in NOD β-cells underscores the role of deamidation in amplifying T-cell reactivity.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:31.864.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aisha Callebaut
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-25 03:18:50	ID requested
1	2022-07-21 12:01:49	announced
⏵ 2	2023-11-14 08:56:32	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: type 1 diabetes, post-translational modification, transglutaminase 2, deamidation

Chantal Mathieu
contact affiliation	Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven
contact email	chantal.mathieu@uzleuven.be
lab head
Aisha Callebaut
contact affiliation	KULeuven
contact email	aisha.callebaut@kuleuven.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034102
     1. Label: PRIDE project
     2. Name: Aberrant expression of transglutaminase 2 in pancreas and thymus of NOD mice underscores the importance of deamidation in neoantigen generation.