TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase
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 T...
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2023
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| Online Access: | http://psasir.upm.edu.my/id/eprint/108707/ https://www.nature.com/articles/s41467-023-42913-z?error=cookies_not_supported&code=9e54cbc1-4279-4a94-9b77-78b1b862a8a9 |
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my.upm.eprints.1087072024-08-09T03:41:24Z http://psasir.upm.edu.my/id/eprint/108707/ TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase Liu, Gang Haw, Tatt Jhong Starkey, Malcolm R. Philp, Ashleigh M. Pavlidis, Stelios Nalkurthi, Christina Nair, Prema M. Gomez, Henry M. Hanish, Irwan Hsu, Alan CY. Hortle, Elinor Pickles, Sophie Rojas-Quintero, Joselyn Estepar, Raul San Jose Marshall, Jacqueline E. Kim, Richard Y. Collison, Adam M. Mattes, Joerg Idrees, Sobia Faiz, Alen Hansbro, Nicole G. Fukui, Ryutaro Murakami, Yusuke Cheng, Hong Sheng Tan, Nguan Soon Chotirmall, Sanjay H. Horvat, Jay C. Foster, Paul S. Oliver, Brian GG. Polverino, Francesca Ieni, Antonio Monaco, Francesco Caramori, Gaetano Sohal, Sukhwinder S. Bracke, Ken R. Wark, Peter A. Adcock, Ian M. Miyake, Kensuke Sin, Don D. Hansbro, Philip M. 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, <jats:italic>TLR7</jats:italic> mRNA is increased in pre-existing datasets from patients with COPD, while TLR7<jats:sup>+</jats:sup> 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. Nature Publishing 2023 Article PeerReviewed Liu, Gang and Haw, Tatt Jhong and Starkey, Malcolm R. and Philp, Ashleigh M. and Pavlidis, Stelios and Nalkurthi, Christina and Nair, Prema M. and Gomez, Henry M. and Hanish, Irwan and Hsu, Alan CY. and Hortle, Elinor and Pickles, Sophie and Rojas-Quintero, Joselyn and Estepar, Raul San Jose and Marshall, Jacqueline E. and Kim, Richard Y. and Collison, Adam M. and Mattes, Joerg and Idrees, Sobia and Faiz, Alen and Hansbro, Nicole G. and Fukui, Ryutaro and Murakami, Yusuke and Cheng, Hong Sheng and Tan, Nguan Soon and Chotirmall, Sanjay H. and Horvat, Jay C. and Foster, Paul S. and Oliver, Brian GG. and Polverino, Francesca and Ieni, Antonio and Monaco, Francesco and Caramori, Gaetano and Sohal, Sukhwinder S. and Bracke, Ken R. and Wark, Peter A. and Adcock, Ian M. and Miyake, Kensuke and Sin, Don D. and Hansbro, Philip M. (2023) TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase. Nature Communications, 14 (1). pp. 1-24. ISSN 2041-1723 https://www.nature.com/articles/s41467-023-42913-z?error=cookies_not_supported&code=9e54cbc1-4279-4a94-9b77-78b1b862a8a9 10.1038/s41467-023-42913-z |
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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, <jats:italic>TLR7</jats:italic> mRNA is increased in pre-existing datasets from patients with COPD, while TLR7<jats:sup>+</jats:sup> 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. |
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Liu, Gang Haw, Tatt Jhong Starkey, Malcolm R. Philp, Ashleigh M. Pavlidis, Stelios Nalkurthi, Christina Nair, Prema M. Gomez, Henry M. Hanish, Irwan Hsu, Alan CY. Hortle, Elinor Pickles, Sophie Rojas-Quintero, Joselyn Estepar, Raul San Jose Marshall, Jacqueline E. Kim, Richard Y. Collison, Adam M. Mattes, Joerg Idrees, Sobia Faiz, Alen Hansbro, Nicole G. Fukui, Ryutaro Murakami, Yusuke Cheng, Hong Sheng Tan, Nguan Soon Chotirmall, Sanjay H. Horvat, Jay C. Foster, Paul S. Oliver, Brian GG. Polverino, Francesca Ieni, Antonio Monaco, Francesco Caramori, Gaetano Sohal, Sukhwinder S. Bracke, Ken R. Wark, Peter A. Adcock, Ian M. Miyake, Kensuke Sin, Don D. Hansbro, Philip M. |
| spellingShingle |
Liu, Gang Haw, Tatt Jhong Starkey, Malcolm R. Philp, Ashleigh M. Pavlidis, Stelios Nalkurthi, Christina Nair, Prema M. Gomez, Henry M. Hanish, Irwan Hsu, Alan CY. Hortle, Elinor Pickles, Sophie Rojas-Quintero, Joselyn Estepar, Raul San Jose Marshall, Jacqueline E. Kim, Richard Y. Collison, Adam M. Mattes, Joerg Idrees, Sobia Faiz, Alen Hansbro, Nicole G. Fukui, Ryutaro Murakami, Yusuke Cheng, Hong Sheng Tan, Nguan Soon Chotirmall, Sanjay H. Horvat, Jay C. Foster, Paul S. Oliver, Brian GG. Polverino, Francesca Ieni, Antonio Monaco, Francesco Caramori, Gaetano Sohal, Sukhwinder S. Bracke, Ken R. Wark, Peter A. Adcock, Ian M. Miyake, Kensuke Sin, Don D. Hansbro, Philip M. TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase |
| author_facet |
Liu, Gang Haw, Tatt Jhong Starkey, Malcolm R. Philp, Ashleigh M. Pavlidis, Stelios Nalkurthi, Christina Nair, Prema M. Gomez, Henry M. Hanish, Irwan Hsu, Alan CY. Hortle, Elinor Pickles, Sophie Rojas-Quintero, Joselyn Estepar, Raul San Jose Marshall, Jacqueline E. Kim, Richard Y. Collison, Adam M. Mattes, Joerg Idrees, Sobia Faiz, Alen Hansbro, Nicole G. Fukui, Ryutaro Murakami, Yusuke Cheng, Hong Sheng Tan, Nguan Soon Chotirmall, Sanjay H. Horvat, Jay C. Foster, Paul S. Oliver, Brian GG. Polverino, Francesca Ieni, Antonio Monaco, Francesco Caramori, Gaetano Sohal, Sukhwinder S. Bracke, Ken R. Wark, Peter A. Adcock, Ian M. Miyake, Kensuke Sin, Don D. Hansbro, Philip M. |
| author_sort |
Liu, Gang |
| title |
TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase |
| title_short |
TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase |
| title_full |
TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase |
| title_fullStr |
TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase |
| title_full_unstemmed |
TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase |
| title_sort |
tlr7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase |
| publisher |
Nature Publishing |
| publishDate |
2023 |
| url |
http://psasir.upm.edu.my/id/eprint/108707/ https://www.nature.com/articles/s41467-023-42913-z?error=cookies_not_supported&code=9e54cbc1-4279-4a94-9b77-78b1b862a8a9 |
| _version_ |
1807051123981287424 |
| score |
13.211869 |