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PXD034102-1

PXD034102 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAberrant expression of transglutaminase 2 in pancreas and thymus of NOD mice underscores the importance of deamidation in neoantigen generation.
DescriptionPost-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.
HostingRepositoryPRIDE
AnnounceDate2022-07-21
AnnouncementXMLSubmission_2022-07-21_12:01:49.312.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAisha Callebaut
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue; deamidated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-05-25 03:18:50ID requested
12022-07-21 12:01:49announced
22023-11-14 08:56:32announced2023-11-14: Updated project metadata.
Publication List
10.3389/FENDO.2022.908248;
Keyword List
submitter keyword: type 1 diabetes, post-translational modification, deamidation, transglutaminase 2
Contact List
Chantal Mathieu
contact affiliationLaboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven
contact emailchantal.mathieu@uzleuven.be
lab head
Aisha Callebaut
contact affiliationKULeuven
contact emailaisha.callebaut@kuleuven.be
dataset submitter
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Dataset FTP location
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