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Promotion of TLR7-MyD88-dependent inflammation and autoimmunity in mice through stem-loop changes in Lnc-Atg16l1

Author

Listed:
  • Zongheng Yang

    (Chinese Academy of Medical Sciences)

  • Shuchen Ji

    (Chinese Academy of Medical Sciences)

  • Lun Liu

    (Chinese Academy of Medical Sciences)

  • Shuo Liu

    (Chinese Academy of Medical Sciences)

  • Bingjing Wang

    (Chinese Academy of Medical Sciences)

  • Yuanwu Ma

    (Chinese Academy of Medical Sciences)

  • Xuetao Cao

    (Chinese Academy of Medical Sciences
    Nankai University
    Navy Medical University)

Abstract

Uncontrolled TLR signaling can cause inflammatory immunopathology and trigger autoimmune diseases. For example, TLR7 promotes pathogenesis of systemic lupus erythematosus. However, whether RNA structural changes affect nucleic acids-sensing TLRs signaling and impact disease progression is unclear. Here by iCLIP-seq we identify a TLR7-binding long non-coding RNA, Lnc-Atg16l1, and find that it promotes TLR7 and other MyD88-dependent TLRs signaling in various types of immune cells. Depletion of Lnc-Atg16l1 attenuates development of TLR7-linked autoimmune phenotypes in the mouse SLE model. Mechanistically, we find that Lnc-Atg16l1 binds to TLR7 at bases near U84 and MyD88 at bases around A129. The analysis of Lnc-Atg16l1 in situ structures show that it strengthens the interaction between TIR domain of TLR7 and MyD88 through specific stem-loop structure changes as a molecular scaffold after TLR7 activation to promote TLR7 downstream signaling. Therefore, we discover a mechanism for host RNA regulation of innate signaling and autoimmune disease through its structural changes. These findings provide insights into the pro-inflammatory function of self RNA in a structure-dependent manner and suggest a potential target for TLR-related autoimmune disorders.

Suggested Citation

  • Zongheng Yang & Shuchen Ji & Lun Liu & Shuo Liu & Bingjing Wang & Yuanwu Ma & Xuetao Cao, 2024. "Promotion of TLR7-MyD88-dependent inflammation and autoimmunity in mice through stem-loop changes in Lnc-Atg16l1," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54674-4
    DOI: 10.1038/s41467-024-54674-4
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