國家衛生研究院 NHRI:Item 3990099045/15474
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    NHRI > Immunology Research Center > Tse-Hua Tan > Periodical Articles >  Item 3990099045/15474


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15474


    Title: DUSP8 induces TGF-beta–stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-Alpha
    Other Titles: DUSP8 induces TGF-β–stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α
    Authors: Chuang, HC;Hsueh, CH;Hsu, PM;Tsai, CY;Shih, YC;Chiu, HY;Chen, YM;Yu, WK;Chen, MH;Tan, TH
    Contributors: Immunology Research Center
    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.
    Date: 2023-11-01
    Relation: Journal of Clinical Investigation. 2023 Nov 01;133(21):Article number e166269.
    Link to: http://dx.doi.org/10.1172/JCI166269
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0021-9738&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001106938100013
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85175877809
    Appears in Collections:[Tse-Hua Tan] Periodical Articles
    [Huai-Chia Chuang] Periodical Articles

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