Nature Communications (Nov 2023)
TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase
- Gang Liu,
- Tatt Jhong Haw,
- Malcolm R. Starkey,
- Ashleigh M. Philp,
- Stelios Pavlidis,
- Christina Nalkurthi,
- Prema M. Nair,
- Henry M. Gomez,
- Irwan Hanish,
- Alan CY. Hsu,
- Elinor Hortle,
- Sophie Pickles,
- Joselyn Rojas-Quintero,
- Raul San Jose Estepar,
- Jacqueline E. Marshall,
- Richard Y. Kim,
- Adam M. Collison,
- Joerg Mattes,
- Sobia Idrees,
- Alen Faiz,
- Nicole G. Hansbro,
- Ryutaro Fukui,
- Yusuke Murakami,
- Hong Sheng Cheng,
- Nguan Soon Tan,
- Sanjay H. Chotirmall,
- Jay C. Horvat,
- Paul S. Foster,
- Brian GG. Oliver,
- Francesca Polverino,
- Antonio Ieni,
- Francesco Monaco,
- Gaetano Caramori,
- Sukhwinder S. Sohal,
- Ken R. Bracke,
- Peter A. Wark,
- Ian M. Adcock,
- Kensuke Miyake,
- Don D. Sin,
- Philip M. Hansbro
Affiliations
- Gang Liu
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Tatt Jhong Haw
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Malcolm R. Starkey
- Depatrment of Immunology and Pathology, Central Clinical School, Monash University
- Ashleigh M. Philp
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Stelios Pavlidis
- The Airways Disease Section, National Heart & Lung Institute, Imperial College London
- Christina Nalkurthi
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Prema M. Nair
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Henry M. Gomez
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Irwan Hanish
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Alan CY. Hsu
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Elinor Hortle
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Sophie Pickles
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Joselyn Rojas-Quintero
- Department of Medicine, Baylor College of Medicine
- Raul San Jose Estepar
- Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School
- Jacqueline E. Marshall
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Richard Y. Kim
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Adam M. Collison
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Joerg Mattes
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Sobia Idrees
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Alen Faiz
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Nicole G. Hansbro
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- Ryutaro Fukui
- Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo
- Yusuke Murakami
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Musashino University
- Hong Sheng Cheng
- Lee Kong Chian School of Medicine, Nanyang Technological University
- Nguan Soon Tan
- Lee Kong Chian School of Medicine, Nanyang Technological University
- Sanjay H. Chotirmall
- Lee Kong Chian School of Medicine, Nanyang Technological University
- Jay C. Horvat
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Paul S. Foster
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Brian GG. Oliver
- Woolcock Institute of Medical Research, University of Sydney & School of Life Sciences, University of Technology
- Francesca Polverino
- Department of Medicine, Baylor College of Medicine
- Antonio Ieni
- Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Anatomic Pathology, Università di Messina
- Francesco Monaco
- Thoracic Surgery, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina
- Gaetano Caramori
- Pneumologia, Dipartimento BIOMORF and Dipartimento di Medicina e Chirurgia, Universities of Messina and Parma
- Sukhwinder S. Sohal
- Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania
- Ken R. Bracke
- Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital
- Peter A. Wark
- Immune Healthy &/or Grow Up Well, Hunter Medical Research Institute & University of Newcastle
- Ian M. Adcock
- School of Clinical Medicine, UNSW Medicine and Health, St Vincent’s Healthcare clinical campus, UNSW
- Kensuke Miyake
- Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo
- Don D. Sin
- The University of British Columbia Centre for Heart Lung Innovation, St Paul’s Hospital & Respiratory Division, Dept of Medicine, University of British Columbia
- Philip M. Hansbro
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney
- DOI
- https://doi.org/10.1038/s41467-023-42913-z
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 24
Abstract
Abstract Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.
