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

Liu, G; Haw, TJ; Starkey, MR; Philp, AM; Pavlidis, S; Nalkurthi, C; Nair, PM; Gomez, HM; Hanish, I; Hsu, AC; Hortle, E; Pickles, S; Rojas-Quintero, J; Estepar, RSJ; Marshall, JE; Kim, RY; Collison, AM; Mattes, J; Idrees, S; Faiz, A; Hansbro, NG; Fukui, R; Murakami, Y; Cheng, HS; Tan, NS; Chotirmall, SH; Horvat, JC; Foster, PS; Oliver, BG; Polverino, F; Ieni, A; Monaco, F; Caramori, G; Sohal, SS; Bracke, KR; Wark, PA; Adcock, IM; Miyake, K; Sin, DD; Hansbro, PM

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

Haw, TJ Starkey, MR Philp, AM Pavlidis, S Nalkurthi, C Nair, PM Gomez, HM Hanish, I Hsu, AC Hortle, E Pickles, S Rojas-Quintero, J Estepar, RSJ Marshall, JE Kim, RY Collison, AM Mattes, J Idrees, S

Faiz, A

Hansbro, NG Fukui, R Murakami, Y Cheng, HS Tan, NS Chotirmall, SH Horvat, JC Foster, PS Oliver, BG Polverino, F Ieni, A Monaco, F Caramori, G Sohal, SS Bracke, KR Wark, PA Adcock, IM Miyake, K Sin, DD Hansbro, PM

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Commun, 2023, 14, (1), pp. 7349
Issue Date:: 2023-11-14

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Field	Value	Language
dc.contributor.author	Liu, G https://orcid.org/0000-0002-0489-2638
dc.contributor.author	Haw, TJ
dc.contributor.author	Starkey, MR
dc.contributor.author	Philp, AM
dc.contributor.author	Pavlidis, S
dc.contributor.author	Nalkurthi, C
dc.contributor.author	Nair, PM
dc.contributor.author	Gomez, HM
dc.contributor.author	Hanish, I
dc.contributor.author	Hsu, AC
dc.contributor.author	Hortle, E
dc.contributor.author	Pickles, S
dc.contributor.author	Rojas-Quintero, J
dc.contributor.author	Estepar, RSJ
dc.contributor.author	Marshall, JE
dc.contributor.author	Kim, RY
dc.contributor.author	Collison, AM
dc.contributor.author	Mattes, J
dc.contributor.author	Idrees, S https://orcid.org/0000-0001-8512-7593
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Hansbro, NG
dc.contributor.author	Fukui, R
dc.contributor.author	Murakami, Y
dc.contributor.author	Cheng, HS
dc.contributor.author	Tan, NS
dc.contributor.author	Chotirmall, SH
dc.contributor.author	Horvat, JC
dc.contributor.author	Foster, PS
dc.contributor.author	Oliver, BG
dc.contributor.author	Polverino, F
dc.contributor.author	Ieni, A
dc.contributor.author	Monaco, F
dc.contributor.author	Caramori, G
dc.contributor.author	Sohal, SS
dc.contributor.author	Bracke, KR
dc.contributor.author	Wark, PA
dc.contributor.author	Adcock, IM
dc.contributor.author	Miyake, K
dc.contributor.author	Sin, DD
dc.contributor.author	Hansbro, PM
dc.date.accessioned	2024-01-16T00:48:06Z
dc.date.available	2023-10-25
dc.date.available	2024-01-16T00:48:06Z
dc.date.issued	2023-11-14
dc.identifier.citation	Nat Commun, 2023, 14, (1), pp. 7349
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/174526
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1137995
dc.relation	http://purl.org/au-research/grants/nhmrc/1023131
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-023-42913-z
dc.rights	info:eu-repo/semantics/openAccess
dc.title	TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
dc.date.updated	2024-01-16T00:42:42Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	1

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/174526