2. Academic Validation
  3. Distinctive CD39+CD9+ lung interstitial macrophages suppress IL-23/Th17-mediated neutrophilic asthma by inhibiting NETosis

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

  • Nat Commun. 2024 Oct 4;15(1):8628. doi: 10.1038/s41467-024-53038-2.
Seunghan Han # 1 2,  Bomin Kim # 1 2,  Do Young Hyeon # 3,  Daeun Jeong 1 2,  Jaechan Ryu 4,  Jae-Sung Nam 5,  Yoon Ha Choi 6,  Bo-Ram Kim 2 7,  Sang Chul Park 8,  Youn Wook Chung 1 2,  Sung Jae Shin 2 7 9,  June-Yong Lee 2 7 9,  Jong Kyoung Kim 6,  Jihye Park 10,  Sei Won Lee 11,  Tae-Bum Kim 12,  Jae Hee Cheon 10,  Hyung-Ju Cho 5,  Chang-Hoon Kim 5,  Joo-Heon Yoon 13,  Daehee Hwang 14,  Ji-Hwan Ryu 15 16
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Korea.
  • 2 Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
  • 3 School of Biological Sciences, Seoul National University, Seoul, Korea.
  • 4 Institut Pasteur, Microenvironment and Immunity Unit, Paris, France.
  • 5 Department of Otorhinolaryngology and Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
  • 6 Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
  • 7 Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Korea.
  • 8 Department of Otorhinolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
  • 9 Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea.
  • 10 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 11 Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 12 Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 13 Department of Otorhinolaryngology and Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea. jhyoon@yuhs.ac.
  • 14 School of Biological Sciences, Seoul National University, Seoul, Korea. daehee@snu.ac.kr.
  • 15 Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Korea. yjh@yuhs.ac.
  • 16 Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. yjh@yuhs.ac.
  • # Contributed equally.
PMID: 39366998 DOI: 10.1038/s41467-024-53038-2
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.

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