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PXD044818-1

PXD044818 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α
DescriptionDual-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.
HostingRepositoryPRIDE
AnnounceDate2023-09-30
AnnouncementXMLSubmission_2023-09-30_06:52:40.434.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHuai-ChiaChuang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-23 23:25:49ID requested
12023-09-30 06:52:40announced
22023-11-14 09:05:07announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: asthma, Pur-α, IL-9, Th9,DUSP8, atopic dermatitis
Contact List
Tse-HuaTan
contact affiliationNational Health Research Institutes, Taiwan
contact emailttan@nhri.edu.tw
lab head
Huai-ChiaChuang
contact affiliationImmunology Research Center, National Health Research Institutes
contact emailcinth@nhri.org.tw
dataset submitter
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Dataset FTP location
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