ArticleThe Journal of clinical investigation2023
DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 9 citations in OpenAlex.
- α‑Cyperone targets the PAK1‑JNK/NF‑κB axis to modulate dendritic cells maturation and Th2/Th9 differentiation in an asthma model.International journal of molecular medicine · 2026Article
- DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.Journal of biomedical science · 2026Review
- Dual specificity protein phosphatase 5, transcriptionally inhibited by SRY-box transcription factor 11, inhibits T helper 2 differentiation in CD4Experimental animals · 2026Article
- MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.The Journal of clinical investigation · 2026Article
- The Transcription Factor DDIT3 Regulates Macrophage Function by Inhibiting KLF10 to Attenuate ALI/ARDS Inflammation.Inflammation · 2026Article
- The Major Role of Type 2 Inflammation in Asthma: From the Perspective of Immunological Mechanism.BioMed research international · 2026Review
- The Pleiotropic IL-9 Network in Asthma Pathogenesis and Targeted Therapy.Journal of inflammation research · 2026Review
- Activation of TSLP-IL-9 Axis Hinders the Antifibrotic Effect of ST2 Deficiency in Pulmonary Fibrosis.International journal of molecular sciences · 2025Article
- Dual-specific phosphatases-8: a new target for clinical disease intervention.Journal of translational medicine · 2025Review
- Mitogen-Activated Protein Kinase Phosphatase-5 is Required for TGF-β Signaling Through a JNK-Dependent Pathway.Molecular and cellular biology · 2025Article
- MAPK Phosphatase-5 is required for TGF-β signaling through a JNK-dependent pathway.bioRxiv : the preprint server for biology · 2024Article
- The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling.Nature communications · 2024Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dual-specificity phosphatase 8 (DUSP8) 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 KO (T-Dusp8 cKO) mice, mass spectrometry analysis, ChIP-Seq, 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 people with asthma and patients with atopic dermatitis. 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.
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