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The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation

Author

Listed:
  • Meng Du

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Lin Yuan

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Xin Tan

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Dandan Huang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Xiaojing Wang

    (Huazhong University of Science and Technology)

  • Zhe Zheng

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Xiaoxiang Mao

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Xiangrao Li

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Liu Yang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Kun Huang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Fengxiao Zhang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Yan Wang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Xi Luo

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Dan Huang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Kai Huang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

Abstract

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRR) with a crucial function in innate immune responses. Activation of TLR4 signaling at the plasma membrane by lipopolysaccharide (LPS) stimulates proinflammatory signaling pathways dependent on the E3 ubiquitin ligase TRAF6. Here we show the LPS-induced long non-coding RNA (lncRNA) Mirt2 functions as a checkpoint to prevent aberrant activation of inflammation, and is a potential regulator of macrophage polarization. Mirt2 associates with, and attenuates Lys63 (K63)-linked ubiquitination of, TRAF6, thus inhibiting activation of NF-κB and MAPK pathways and limiting production of proinflammatory cytokines. Adenovirus mediated gene transfer of Mirt2 protects mice from endotoxemia induced fatality and multi-organ dysfunction. These findings identify lncRNA Mirt2 as a negative feedback regulator of excessive inflammation.

Suggested Citation

  • Meng Du & Lin Yuan & Xin Tan & Dandan Huang & Xiaojing Wang & Zhe Zheng & Xiaoxiang Mao & Xiangrao Li & Liu Yang & Kun Huang & Fengxiao Zhang & Yan Wang & Xi Luo & Dan Huang & Kai Huang, 2017. "The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02229-1
    DOI: 10.1038/s41467-017-02229-1
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