한빛사논문
Seunghan Han1,2,13, Bomin Kim1,2,13, Do Young Hyeon3,13, Daeun Jeong1,2, Jaechan Ryu4, Jae-Sung Nam5, Yoon Ha Choi6, Bo-Ram Kim2,7, Sang Chul Park8, Youn Wook Chung1,2, Sung Jae Shin2,7,9, June-Yong Lee2,7,9, Jong Kyoung Kim6, Jihye Park10, Sei Won Lee11, Tae-Bum Kim12, Jae Hee Cheon10, Hyung-Ju Cho5, Chang-Hoon Kim5, Joo-Heon Yoon5, Daehee Hwang3 & Ji-Hwan Ryu1,2
1Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Korea.
2Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
3School of Biological Sciences, Seoul National University, Seoul, Korea.
4Institut Pasteur, Microenvironment and Immunity Unit, Paris, France.
5Department of Otorhinolaryngology and Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
6Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea.
7Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Korea.
8Department of Otorhinolaryngology–Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
9Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea.
10Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
11Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
12Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
13These authors contributed equally: Seunghan Han, Bomin Kim, Do Young Hyeon.
Corresponding authors
Correspondence to Joo-Heon Yoon, Daehee Hwang or Ji-Hwan Ryu.
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.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기