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http://ir.nhri.org.tw/handle/3990099045/15474
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| 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: | [譚澤華] 期刊論文
[莊懷佳] 期刊論文
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| SCP85175877809.pdf | | 2874Kb | Adobe PDF | 110 | View/Open |
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