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...

Full description

Saved in:

Bibliographic Details
Published in:	Nature communications Vol. 14; no. 1; p. 7349
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 14-11-2023 Nature Publishing Group Nature Portfolio
Subjects:	13/2 13/51 14/35 38/77 45/90 49/61 631/250/24/2510 631/250/256/2515 631/250/262/2106/2108 692/699/1785/4037 Animal models Chronic obstructive pulmonary disease Cigarette smoke Cigarettes Emphysema Humanities and Social Sciences Imiquimod Immune system Inhalation Innate immunity Lung diseases Lungs Mast cells Monoclonal antibodies mRNA multidisciplinary Obstructive lung disease Proteins Respiration RNA viruses Science Science (multidisciplinary) Smoke Therapeutic targets TLR7 protein Toll-like receptors Tryptase
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. Toll-like receptor 7 (TLR7) normally recognizes exogenous single-stranded RNA for the activation of innate immunity. Here the authors show that TLR7 may also contribute, via the modulation of mast cell functions, to experimental, cigarette smoke-induced mouse models of emphysema, thereby hinting TLR7 as a potential therapeutic target for human lung inflammation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-023-42913-z