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Distinctive CD39+CD9+ lung interstitial macrophages suppress IL-23/Th17-mediated neutrophilic asthma by inhibiting NETosis

Author

Listed:
  • Seunghan Han

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Bomin Kim

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Do Young Hyeon

    (Seoul National University)

  • Daeun Jeong

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Jaechan Ryu

    (Microenvironment and Immunity Unit)

  • Jae-Sung Nam

    (Yonsei University College of Medicine)

  • Yoon Ha Choi

    (Pohang University of Science and Technology)

  • Bo-Ram Kim

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Sang Chul Park

    (Hallym University College of Medicine)

  • Youn Wook Chung

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Sung Jae Shin

    (Yonsei University College of Medicine
    Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • June-Yong Lee

    (Yonsei University College of Medicine
    Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Jong Kyoung Kim

    (Pohang University of Science and Technology)

  • Jihye Park

    (Yonsei University College of Medicine)

  • Sei Won Lee

    (University of Ulsan College of Medicine)

  • Tae-Bum Kim

    (University of Ulsan College of Medicine)

  • Jae Hee Cheon

    (Yonsei University College of Medicine)

  • Hyung-Ju Cho

    (Yonsei University College of Medicine)

  • Chang-Hoon Kim

    (Yonsei University College of Medicine)

  • Joo-Heon Yoon

    (Yonsei University College of Medicine)

  • Daehee Hwang

    (Seoul National University)

  • Ji-Hwan Ryu

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

Abstract

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39+CD9+ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39+CD9+ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39+CD9+ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39+CD9+ IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39+CD9+ IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.

Suggested Citation

  • Seunghan Han & Bomin Kim & Do Young Hyeon & Daeun Jeong & Jaechan Ryu & Jae-Sung Nam & Yoon Ha Choi & Bo-Ram Kim & Sang Chul Park & Youn Wook Chung & Sung Jae Shin & June-Yong Lee & Jong Kyoung Kim & , 2024. "Distinctive CD39+CD9+ lung interstitial macrophages suppress IL-23/Th17-mediated neutrophilic asthma by inhibiting NETosis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53038-2
    DOI: 10.1038/s41467-024-53038-2
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