國家衛生研究院 NHRI:Item 3990099045/11325
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    題名: Blimp-1-mediated pathway promotes type I IFN production in plasmacytoid dendritic cells by targeting to interleukin-1 receptor-associated kinase M
    作者: Ko, YA;Chan, YH;Liu, CH;Liang, JJ;Chuang, TH;Hsueh, YP;Lin, YL;Lin, KI
    貢獻者: Immunology Research Center
    摘要: Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs capable of rapidly producing copious amounts of type I IFN (IFN-I) in response to viral infections. The mechanism regulating rapid production of IFN-I after pDCs are exposed to viral nucleic acids remains elusive. Here, we show that the transcription factor Blimp-1 is promptly induced in pDCs after exposure to TLR7 and TLR9 ligands via a unique Ras-related C3 botulinum toxin substrate (Rac)-mediated pathway. Deletion of the Prdm1 gene encoding Blimp-1 impaired production of IFN-I, but not other cytokines, upon viral infection or treatment with CpG DNA in pDCs. Accordingly, mice lacking Blimp-1 in DCs failed to produce IFN-I after CpG stimulation and did not mount proper antiviral responses following flavivirus infection. The development of pDCs in bone marrow as well as the induction of several activation markers, such as CD86, CD69, and MHCII, by CpG stimulation was generally not affected by the absence of Blimp-1. Mechanistically, we found that Blimp-1 controls the activation of IKKalpha and IRF7 by directly suppressing interleukin-1 receptor-associated kinase 3 (Irak3), a negative regulator of TLR signaling, in pDCs. Together, we identify a Blimp-1-dependent pathway that rapidly facilitates IFN-I production by relieving interleukin-1 receptor-associated kinase M, encoded by Irak3, in pDCs.
    日期: 2018-08-07
    關聯: Frontiers in Immunology. 2018 Aug 7;9:Article number 828.
    Link to: http://dx.doi.org/10.3389/fimmu.2018.01828
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1664-3224&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000441051100001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85054929777
    顯示於類別:[莊宗顯] 期刊論文

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