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TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase

Author

Listed:
  • Gang Liu

    (University of Technology Sydney)

  • Tatt Jhong Haw

    (Hunter Medical Research Institute & University of Newcastle)

  • Malcolm R. Starkey

    (Monash University)

  • Ashleigh M. Philp

    (University of Technology Sydney
    UNSW Medicine and Health, St Vincent’s Healthcare clinical campus, UNSW)

  • Stelios Pavlidis

    (Imperial College London)

  • Christina Nalkurthi

    (University of Technology Sydney)

  • Prema M. Nair

    (Hunter Medical Research Institute & University of Newcastle)

  • Henry M. Gomez

    (Hunter Medical Research Institute & University of Newcastle)

  • Irwan Hanish

    (Hunter Medical Research Institute & University of Newcastle
    Universiti Putra Malaysia)

  • Alan CY. Hsu

    (Hunter Medical Research Institute & University of Newcastle)

  • Elinor Hortle

    (University of Technology Sydney)

  • Sophie Pickles

    (University of Technology Sydney)

  • Joselyn Rojas-Quintero

    (Baylor College of Medicine)

  • Raul San Jose Estepar

    (Harvard Medical School)

  • Jacqueline E. Marshall

    (University of Technology Sydney)

  • Richard Y. Kim

    (Hunter Medical Research Institute & University of Newcastle
    University of Technology Sydney)

  • Adam M. Collison

    (Hunter Medical Research Institute & University of Newcastle)

  • Joerg Mattes

    (Hunter Medical Research Institute & University of Newcastle)

  • Sobia Idrees

    (University of Technology Sydney)

  • Alen Faiz

    (University of Technology Sydney)

  • Nicole G. Hansbro

    (University of Technology Sydney)

  • Ryutaro Fukui

    (The University of Tokyo)

  • Yusuke Murakami

    (Musashino University)

  • Hong Sheng Cheng

    (Nanyang Technological University)

  • Nguan Soon Tan

    (Nanyang Technological University
    Nanyang Technological University)

  • Sanjay H. Chotirmall

    (Nanyang Technological University
    Tan Tock Seng Hospital)

  • Jay C. Horvat

    (Hunter Medical Research Institute & University of Newcastle)

  • Paul S. Foster

    (Hunter Medical Research Institute & University of Newcastle)

  • Brian GG. Oliver

    (University of Sydney & School of Life Sciences, University of Technology)

  • Francesca Polverino

    (Baylor College of Medicine)

  • Antonio Ieni

    (Università di Messina)

  • Francesco Monaco

    (Università di Messina)

  • Gaetano Caramori

    (Universities of Messina and Parma)

  • Sukhwinder S. Sohal

    (University of Tasmania)

  • Ken R. Bracke

    (Ghent University Hospital)

  • Peter A. Wark

    (Hunter Medical Research Institute & University of Newcastle)

  • Ian M. Adcock

    (UNSW Medicine and Health, St Vincent’s Healthcare clinical campus, UNSW)

  • Kensuke Miyake

    (The University of Tokyo)

  • Don D. Sin

    (University of British Columbia)

  • Philip M. Hansbro

    (University of Technology Sydney
    Hunter Medical Research Institute & University of Newcastle)

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.

Suggested Citation

  • 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 Pick, 2023. "TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42913-z
    DOI: 10.1038/s41467-023-42913-z
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    References listed on IDEAS

    as
    1. Louisa L. Y. Chan & Danielle E. Anderson & Hong Sheng Cheng & Fransiskus Xaverius Ivan & Si Chen & Adrian E. Z. Kang & Randy Foo & Akshamal M. Gamage & Pei Yee Tiew & Mariko Siyue Koh & Ken Cheah Hooi, 2022. "The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Maor Sauler & John E. McDonough & Taylor S. Adams & Neeharika Kothapalli & Thomas Barnthaler & Rhiannon B. Werder & Jonas C. Schupp & Jessica Nouws & Matthew J. Robertson & Cristian Coarfa & Tao Yang , 2022. "Characterization of the COPD alveolar niche using single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Eunice E. To & Ross Vlahos & Raymond Luong & Michelle L. Halls & Patrick C. Reading & Paul T. King & Christopher Chan & Grant R. Drummond & Christopher G. Sobey & Brad R. S. Broughton & Malcolm R. Sta, 2017. "Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    4. Atsuo Kanno & Natsuko Tanimura & Masayuki Ishizaki & Kentaro Ohko & Yuji Motoi & Masahiro Onji & Ryutaro Fukui & Takaichi Shimozato & Kazuhide Yamamoto & Takuma Shibata & Shigetoshi Sano & Akiko Sugah, 2015. "Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
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