PXD044818-2

PXD044818 is an original dataset announced via ProteomeXchange.

Title	DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α
Description	Dual-specificity phosphatase 8 is a MAPK phosphatase that dephosphorylates and inactivates the kinase JNK. DUSP8 is highly expressed in T cells; however, the in vivo role of DUSP8 in T cells remains unclear. Using T-cell-specific DUSP8 conditional knockout (T-DUSP8 cKO) mice, mass spectrometry analysis, chromatin-immunoprecipitation sequencing, and immune analysis, we found that DUSP8 interacted with Pur-α, stimulated interleukin-9 (IL-9) gene expression, and promoted Th9 differentiation. Mechanistically, DUSP8 dephosphorylated the transcriptional repressor Pur-α upon TGF-β signaling, leading to the nuclear export of Pur-α and subsequent IL-9 transcriptional activation. Furthermore, IL-9 mRNA levels were induced in Pur-α-deficient T cells. In addition, T-DUSP8 cKO mice displayed reduction of IL-9 and Th9-mediated immune responses in the allergic asthma model. Reduction of IL-9 mRNA levels in T cells and allergic responses of T-DUSP8 cKO mice was reversed by Pur-α knockout. Remarkably, DUSP8 protein levels and the DUSP8–Pur-α interaction were indeed increased in the cytoplasm of T cells from human asthma patients and atopic dermatitis patients. Collectively, DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-induced allergic responses by inhibiting the nuclear translocation of the transcriptional repressor Pur-α. DUSP8 may be a T-cell biomarker and therapeutic target for asthma and atopic dermatitis.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:05:07.444.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Huai-Chia Chuang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 23:25:49	ID requested
1	2023-09-30 06:52:40	announced
⏵ 2	2023-11-14 09:05:07	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: asthma, Pur-α, IL-9, Th9,DUSP8, atopic dermatitis

Tse-Hua Tan
contact affiliation	National Health Research Institutes, Taiwan
contact email	ttan@nhri.edu.tw
lab head
Huai-Chia Chuang
contact affiliation	Immunology Research Center, National Health Research Institutes
contact email	cinth@nhri.org.tw
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/09/PXD044818

PRIDE project URI

• PRIDE
  1. PXD044818
     1. Label: PRIDE project
     2. Name: DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α