PXD008608

PXD008608 is an original dataset announced via ProteomeXchange.

Title	A new life-saving role for Glucocorticoid Receptor dimers: repressing STAT1-induced IFN response in the gut
Description	The use of glucocorticoids (GCs), which bind and activate the glucocorticoid receptor (GR), in systemic inflammatory response syndromes (SIRS) is disputed. Mice with a poor transcriptional response of dimer-dependent GR target genes were studied in a model of TNF-induced SIRS. These GR dim/dim mice display a significant increase in TNF sensitivity and a lack of protection by the GC dexamethasone (DEX). Unchallenged GR dim/dim mice have a strong interferon-stimulated gene (ISG) signature at the transcriptional level and this ISG signature is gut specific. Here, we used shotgun proteomics to study the regulation of ISG proteins in the ileum of GR dim/dim mice. Our data showed that unchallenged GR dim/dim mice have a strong interferon-stimulated gene (ISG) signature, along with STAT1 upregulation. Taken together, we show that GR dim/dim mice poorly control ISG expression resulting in excessive necroptosis induction by TNF. Our findings support a critical interplay between gut microbiota, interferons, necroptosis and GR in both the basal response to acute inflammatory challenges and in the pharmacological intervention by GCs.
HostingRepository	PRIDE
AnnounceDate	2019-04-01
AnnouncementXML	Submission_2019-04-01_00:51:20.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabien Thery
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-08 01:54:59	ID requested
⏵ 1	2019-04-01 00:51:22	announced

Ballegeer M, Van Looveren K, Timmermans S, Eggermont M, Vandevyver S, Thery F, Dendoncker K, Souffriau J, Vandewalle J, Van Wyngene L, De Rycke R, Takahashi N, Vandenabeele P, Tuckermann J, Reichardt HM, Impens F, Beyaert R, De Bosscher K, Vandenbroucke RE, Libert C, Glucocorticoid receptor dimers control intestinal STAT1 and TNF-induced inflammation in mice. J Clin Invest, 128(8):3265-3279(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: shotgun proteomics, murine ileum, inflammatory response, ISG, SIRS

Claude Libert
contact affiliation	VIB-UGent Center for Inflammation Research, Ghent University, Belgium
contact email	Claude.Libert@irc.vib-UGent.be
lab head
Fabien Thery
contact affiliation	VIB-UGent
contact email	fabien.thery91@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008608
     1. Label: PRIDE project
     2. Name: A new life-saving role for Glucocorticoid Receptor dimers: repressing STAT1-induced IFN response in the gut