國家衛生研究院 NHRI:Item 3990099045/14129
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 916263      線上人數 : 1399
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/14129


    題名: PERK is a critical metabolic hub for immunosuppressive function in macrophages
    作者: Raines, LN;Zhao, HX;Wang, YZ;Chen, HY;Gallart-Ayala, H;Hsueh, PC;Cao, W;Koh, Y;Alamonte-Loya, A;Liu, PS;Ivanisevic, J;Lio, CWJ;Ho, PC;Huang, SCC
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation. Loss of PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. PERK activation mediated the upregulation of phosphoserine aminotransferase 1 (PSAT1) and serine biosynthesis via the downstream transcription factor ATF-4. Increased serine biosynthesis resulted in enhanced mitochondrial function and alpha-ketoglutarate production required for JMJD3-dependent epigenetic modification. Inhibition of PERK suppressed macrophage immunosuppressive activity and could enhance the efficacy of immune checkpoint programmed cell death protein 1 inhibition in melanoma. Our findings delineate a previously undescribed connection between PERK signaling and PSAT1-mediated serine metabolism critical for promoting immunosuppressive function in M2 macrophages.
    日期: 2022-02-28
    關聯: Nature Immunology. 2022 Feb 28;23(3):431-445.
    Link to: http://dx.doi.org/10.1038/s41590-022-01145-x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1529-2908&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000762163700003
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85125317692
    顯示於類別:[劉卜慈] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    ISI000762163700003.pdf11258KbAdobe PDF231檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋