- Title
- TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase
- Creator
- Liu, Gang; Haw, Tatt Jhong; 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; Starkey, Malcolm R.; Hansbro, Nicole G.; Fukui, R; Murakami, Y; Cheng, HS; Tan, NS; Chotirmall, SH; Horvat, Jay C.; Foster, Paul S.; Oliver, BG; Polverino, F; Philp, Ashleigh M.; Ieni, A; Monaco, F; Caramori, G; Sohal, SS; Bracke, KR; Wark, Peter A.; Adcock, IM; Miyake, K; Sin, DD; Hansbro, Philip M.; Pavlidis, Stelios; Nalkurthi, Christina; Nair, Prema M.; Gomez, Henry M.; Hanish, Irwan; Hsu, Alan CY
- Relation
- NHMRC.1137995 http://purl.org/au-research/grants/nhmrc/1137995 | 1023131 http://purl.org/au-research/grants/nhmrc/1023131 | ARC DE170100226 http://purl.org/au-research/grants/arc/DE170100226
- Relation
- Nature Communications Vol. 14, no. 7349
- Publisher Link
- http://dx.doi.org/10.1038/s41467-023-42913-z
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- toll-like receptor 7 (TLR7); lung; cigarette smoke; chronic obstructive pulmonary disease (COPD); SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1500557
- Identifier
- uon:54960
- Identifier
- ISSN:2041-1723
- Rights
- © Crown 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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