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Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice

Author

Listed:
  • Bing Xie

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

  • Mengyuan Wang

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

  • Xinyu Zhang

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

  • Yujing Zhang

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

  • Hong Qi

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

  • Hong Liu

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

  • Yuming Wu

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

  • Xiaoyue Wen

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

  • Xiaoyan Chen

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

  • Mengqi Han

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

  • Dan Xu

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

  • Xueqiang Sun

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

  • Xue Zhang

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

  • Xin Zhao

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

  • You Shang

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

  • Shiying Yuan

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

  • Jiancheng Zhang

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

Abstract

Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C– IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/β-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.

Suggested Citation

  • Bing Xie & Mengyuan Wang & Xinyu Zhang & Yujing Zhang & Hong Qi & Hong Liu & Yuming Wu & Xiaoyue Wen & Xiaoyan Chen & Mengqi Han & Dan Xu & Xueqiang Sun & Xue Zhang & Xin Zhao & You Shang & Shiying Yu, 2024. "Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51209-9
    DOI: 10.1038/s41467-024-51209-9
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    References listed on IDEAS

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    3. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
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