2. Academic Validation
  3. Eosinophils promote pulmonary matrix destruction and emphysema via Cathepsin L

Eosinophils promote pulmonary matrix destruction and emphysema via Cathepsin L

  • Signal Transduct Target Ther. 2023 Oct 11;8(1):390. doi: 10.1038/s41392-023-01634-x.
Xia Xu 1,  Tao Yu 2,  Lingling Dong 3,  Rainer Glauben 4,  Siyuan Wu 1,  Ronghua Huang 1,  Shiwei Qumu 2 5,  Chenli Chang 5,  Jing Guo 6,  Lin Pan 6,  Ting Yang 2 5,  Xin Lin 7,  Ke Huang 8 9,  Zhihua Chen 10,  Chen Wang 11 12 13
Affiliations

Affiliations

  • 1 Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  • 2 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
  • 3 Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 4 Department of Gastroenterology, Infectious Diseases, and Rheumatology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany.
  • 5 Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.
  • 6 Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
  • 7 Institute for Immunology, Tsinghua University School of Medicine, Beijing, China.
  • 8 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China. huangke_zryy@163.com.
  • 9 Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China. huangke_zryy@163.com.
  • 10 Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. zhihuachen@zju.edu.cn.
  • 11 Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. cyh-birm@263.net.
  • 12 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China. cyh-birm@263.net.
  • 13 Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China. cyh-birm@263.net.
PMID: 37816708 DOI: 10.1038/s41392-023-01634-x
Abstract

Patients with chronic obstructive pulmonary disease (COPD) who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema. This implies the potential involvement of eosinophils in the development of emphysema. However, the precise mechanisms underlying the development of eosinophil-mediated emphysema remain unclear. In this study, we employed single-cell RNA Sequencing to identify eosinophil subgroups in mouse models of asthma and emphysema, followed by functional analyses of these subgroups. Assessment of accumulated eosinophils unveiled distinct transcriptomes in the lungs of mice with elastase-induced emphysema and ovalbumin-induced asthma. Depletion of eosinophils through the use of anti-interleukin-5 Antibodies ameliorated elastase-induced emphysema. A particularly noteworthy discovery is that eosinophil-derived Cathepsin L contributed to the degradation of the extracellular matrix, thereby leading to emphysema in pulmonary tissue. Inhibition of Cathepsin L resulted in a reduction of elastase-induced emphysema in a mouse model. Importantly, eosinophil levels correlated positively with serum Cathepsin L levels, which were higher in emphysema patients than those without emphysema. Expression of Cathepsin L in eosinophils demonstrated a direct association with lung emphysema in COPD patients. Collectively, these findings underscore the significant role of eosinophil-derived Cathepsin L in extracellular matrix degradation and remodeling, and its relevance to emphysema in COPD patients. Consequently, targeting eosinophil-derived Cathepsin L could potentially offer a therapeutic avenue for emphysema patients. Further investigations are warranted to explore therapeutic strategies targeting Cathepsin L in emphysema patients.

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