PXD063776

PXD063776 is an original dataset announced via ProteomeXchange.

Title	A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains homeostatic Th17 cell state
Description	T helper 17 (Th17) cells are heterogeneous; homeostatic Th17 (Th17Hom) cells maintain tissue homeostasis and pro-inflammatory Th17 (Th17Inf) cells drive autoimmune inflammation. IL-23 drives Th17Inf, but the signals that maintain Th17Hom remain unclear. Here, we found that differential glucocorticoid (GC) production downstream of CYP11A1, a critical enzyme for steroidogenesis, distinguished Th17Hom cells from Th17Inf cells. Although TCR signaling opened the Cyp11a1 locus, TGFβ1 and IL-6, key cytokines for Th17Hom cell differentiation, maintained and amplified Cyp11a1. Th17Hom cell-derived GC signaled through the glucocorticoid receptor (GR), which was higher in Th17Hom cells compared to Th17Inf cells, thereby forming a circuit that maintained the homeostatic state. Integration of multi-omics data from CYP11A1- and GR-deficient Th17Hom cells revealed a gene network underlying this circuit. TGFβ1, a key node in the network, restored GC sensing to Th17Inf. We thus identify a GC signaling circuit that maintains Th17 homeostasis with implications for treating Th17-mediated autoimmunity.
HostingRepository	PRIDE
AnnounceDate	2026-06-12
AnnouncementXML	Submission_2026-06-12_11:55:51.116.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 12:24:56	ID requested
⏵ 1	2026-06-12 11:55:51	announced

10.1016/J.IMMUNI.2026.05.015;

submitter keyword: Th17, glucocorticoid,CYP11A1, homeostasis, TGFβ1, CNS autoimmunity

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. PXD063776
     1. Label: PRIDE project
     2. Name: A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains homeostatic Th17 cell state