IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-09903-6.html
   My bibliography  Save this article

Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation

Author

Listed:
  • Huamin Wang

    (Peking Union Medical College, Chinese Academy of Medical Sciences
    Second Military Medical University
    Nankai University)

  • Xiang Hu

    (Peking Union Medical College, Chinese Academy of Medical Sciences
    Second Military Medical University
    Zhejiang University School of Medicine)

  • Mingyan Huang

    (Second Military Medical University)

  • Juan Liu

    (Second Military Medical University)

  • Yan Gu

    (Second Military Medical University)

  • Lijia Ma

    (Westlake Institute for Advanced Study)

  • Qi Zhou

    (Institute of Zoology, Chinese Academy of Sciences)

  • Xuetao Cao

    (Peking Union Medical College, Chinese Academy of Medical Sciences
    Second Military Medical University
    Nankai University
    Zhejiang University School of Medicine)

Abstract

N6-methyladenosine (m6A) modification plays important roles in various cellular responses by regulating mRNA biology. However, how m6A modification is involved in innate immunity via affecting the translation of immune transcripts remains to be further investigated. Here we report that RNA methyltransferase Mettl3-mediated mRNA m6A methylation promotes dendritic cell (DC) activation and function. Specific depletion of Mettl3 in DC resulted in impaired phenotypic and functional maturation of DC, with decreased expression of co-stimulatory molecules CD40, CD80 and cytokine IL-12, and reduced ability to stimulate T cell responses both in vitro and in vivo. Mechanistically, Mettl3-mediated m6A of CD40, CD80 and TLR4 signaling adaptor Tirap transcripts enhanced their translation in DC for stimulating T cell activation, and strengthening TLR4/NF-κB signaling-induced cytokine production. Our findings identify a new role for Mettl3-mediated m6A modification in increasing translation of certain immune transcripts for physiological promotion of DC activation and DC-based T cell response.

Suggested Citation

  • Huamin Wang & Xiang Hu & Mingyan Huang & Juan Liu & Yan Gu & Lijia Ma & Qi Zhou & Xuetao Cao, 2019. "Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09903-6
    DOI: 10.1038/s41467-019-09903-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-09903-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-09903-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Cristina Leoni & Marian Bataclan & Taku Ito-Kureha & Vigo Heissmeyer & Silvia Monticelli, 2023. "The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Wen-Lan Yang & Weinan Qiu & Ting Zhang & Kai Xu & Zi-Juan Gu & Yu Zhou & Heng-Ji Xu & Zhong-Zhou Yang & Bin Shen & Yong-Liang Zhao & Qi Zhou & Ying Yang & Wei Li & Peng-Yuan Yang & Yun-Gui Yang, 2023. "Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09903-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.