PXD071790

PXD071790 is an original dataset announced via ProteomeXchange.

Title	CCL20-CCR6 signaling alters the metabolic reprogramming to promote the pathogenic Th17 cell differentiation
Description	Chemokine receptor CCR6 is a G-protein-coupled receptor that binds its high-affinity ligand, CCL20. Among the CD4+ T cells, Th17 and regulatory T cells express CCR6, which facilitates their migration in CCL20-enriched, inflamed tissue. Migration of CCR6+ T cells from secondary lymphoid tissues into inflamed tissues exposes them to a distinct metabolic microenvironment. What drives the metabolic adaptation of cells in these tissues and what contributes to their effector or regulatory function is not clearly understood. During colitis, increased gut production of CCL20 promotes the recruitment of these cells. We demonstrated that the intrinsic signaling of CCL20-CCR6 in CD4+ T cells promotes the differentiation of inflamatory Th1-like Th17 cells (T-bet+RORγt+) during colitis in both mouse models and humans. This signaling induces rapamycin-sensitive phosphorylation of PI3K, Akt, mTORC1, and STAT3 in a CCR6-dependent manner. RNA-seq and proteomics analysis revealed alterations in CCL20 during Th17 differentiation, affecting several metabolic pathways, including energy metabolism. CCL20 significantly increased glycolysis and inhibited oxidative phosphorylation, thereby driving the differentiation of pathogenic Th17 cells. Our findings suggest that alterations in CCR6-induced changes in Th17 metabolism offer an interesting therapeutic target for gut inflammation and autoimmunity.
HostingRepository	PRIDE
AnnounceDate	2025-12-10
AnnouncementXML	Submission_2025-12-09_19:58:40.479.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD071790
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Girdhari Lal
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-09 17:52:50	ID requested
⏵ 1	2025-12-09 19:58:41	announced

10.1016/J.ISCI.2025.114385;

10.6019/PXD071790;

submitter keyword: CCR6

Th17 cells

Ulcerative colitis

Chemokine receptor

Dr.Girdhari Lal
contact affiliation	BRIC-National Centre for Cell Science, Pune
contact email	glal@nccs.res.in
lab head
Girdhari Lal
contact affiliation	BRIC-National Centre for Cell Science, Pune
contact email	glal@nccs.res.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071790
     1. Label: PRIDE project
     2. Name: CCL20-CCR6 signaling alters the metabolic reprogramming to promote the pathogenic Th17 cell differentiation