PXD063778

PXD063778 is an original dataset announced via ProteomeXchange.

Title	Interleukin-23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity
Description	Interleukin-23 receptor (IL-23R) signaling is critical for the generation of pro-inflammatory CD4+ IL-17-producing T cells (Th17) that can drive autoimmune tissue inflammation, but the underlying mechanisms are not clear. We integrated phosphoproteomic and transcriptomic data downstream of IL-23R and IL-12R, which share a common subunit, to identify mechanisms engaged specifically by IL-23. We identified chromodomain helicase DNA-binding protein 1 (CHD1), an epigenetic regulator, and the glucocorticoid receptor (GR), a transcription factor (TF), as mediators of IL-23R signaling. IL-23R activation promoted CHD1 interaction with TF STAT3 and co-binding at the TF RORγt locus to enforce a pro-inflammatory Th17 state. Conversely, IL-23R signaling altered phosphorylation of the GR, thereby preventing its activation and nuclear translocation, ultimately impairing GR-driven inhibition of pro-inflammatory Th17 gene programs. Our findings uncover two mechanisms by which IL-23 promotes a pro-inflammatory Th17 cell state, offering potential therapeutic targets for treating Th17-driven autoimmune tissue inflammation and restoring homeostasis.
HostingRepository	PRIDE
AnnounceDate	2026-06-12
AnnouncementXML	Submission_2026-06-12_12:06:46.944.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuyang Han
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-08 13:20:02	ID requested
⏵ 1	2026-06-12 12:06:47	announced

10.1016/J.IMMUNI.2026.05.016;

submitter keyword: CHD1, EAE, IL-23R, GR, Proteomics,Th17

Ana Carrizosa Anderson
contact affiliation	The Gene Lay Institute of Immunology and Inflammation Harvard Medical School and Brigham and Women's Hospital
contact email	acanderson@bwh.harvard.edu
lab head
Yuyang Han
contact affiliation	Brigham and Women's Hospital
contact email	yhan8@bwh.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063778
     1. Label: PRIDE project
     2. Name: Interleukin-23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity