IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42913-z.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42913-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42913-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. 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.
    3. Sanem Sariyar & Alexandros Sountoulidis & Jan Niklas Hansen & Sergio Marco Salas & Mariya Mardamshina & Anna Martinez Casals & Frederic Ballllosera Navarro & Zaneta Andrusivova & Xiaofei Li & Paulo Cz, 2024. "High-parametric protein maps reveal the spatial organization in early-developing human lung," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42913-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.