: 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.

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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 14:1(2023), p. 7349. [10.1038/s41467-023-42913-z]

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

Caramori, Gaetano
Membro del Collaboration Group
;
2023-01-01

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.
2023
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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 14:1(2023), p. 7349. [10.1038/s41467-023-42913-z]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2964952
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact