國家衛生研究院 NHRI:Item 3990099045/15584
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    題名: DUSP8 induces TGF-Beta-stimulated IL-9 transcription and Th9-mediated immune responses by inactivating a transcriptional repressor
    其他題名: DUSP8 induces TGF-ß-stimulated IL-9 transcription and Th9-mediated immune responses by inactivating a transcriptional repressor
    作者: Chuang, HC;Tan, TH
    貢獻者: Immunology Research Center
    摘要: 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 vivorole of DUSP8 in T cells remains unclear. Using T-cell-specific DUSP8 conditional knockout (T-DUSP8 cKO, DUSP8 f/f;CD4-Cre) mice, mass spectrometry, and chromatin-immunoprecipitation sequencing, we found that DUSP8 stimulated interleukin-9 (IL-9) gene expression and Th9 differentiation. TGF-β stimulated DUSP8 phosphatase activity in T cells. Mechanistically, DUSP8 dephosphorylated a transcriptional repressor upon TGF-β signaling, leading to the nuclear export of this transcriptional repressor and subsequent IL-9 transcriptional activation. Reduction of IL-9 mRNA levels in T cells of T-DUSP8 cKO mice was reversed by knocking out the transcriptional repressor in double knockout mice. Furthermore, IL-9 mRNA levels were induced in T cells lacking the transcriptional repressor. In addition, T-DUSP8 cKO mice displayed a reduction of IL-9 and Th9-mediated immune responses of allergy, autoimmune responses, and anti-tumor immunity in animal models. In contrast, the reduced allergy phenotype in T-DUSP8 cKO mice was reversed by knocking out the transcriptional repressor in double knockout mice. Collectively, DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated immune responses by promoting the nuclear export of a transcriptional repressor.
    日期: 2023-05-01
    關聯: Journal of Immunology. 2023 May 01;210(Suppl. 1):Abstract number 243.04.
    Link to: http://dx.doi.org/10.4049/jimmunol.210.Supp.243.04
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
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