PXD044818 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-09-30 |
AnnouncementXML | Submission_2023-09-30_06:52:40.434.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Huai-ChiaChuang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ Orbitrap Velos |
Dataset History
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. |
Publication List
Keyword List
submitter keyword: asthma, Pur-α, IL-9, Th9,DUSP8, atopic dermatitis |
Contact List
Tse-HuaTan |
contact affiliation | National Health Research Institutes, Taiwan |
contact email | ttan@nhri.edu.tw |
lab head | |
Huai-ChiaChuang |
contact affiliation | Immunology Research Center, National Health Research Institutes |
contact email | cinth@nhri.org.tw |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044818
- Label: PRIDE project
- Name: DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α