HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling.

Loh, Z; Simpson, J; Ullah, A; Zhang, V; Gan, WJ; Lynch, JP; Werder, RB; Sikder, AA; Lane, K; Sim, CB; Porrello, E; Mazzone, SB; Sly, PD; Steptoe, RJ; Spann, KM; Sukkar, MB; Upham, JW; Phipps, S

HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling.

Loh, Z Simpson, J Ullah, A Zhang, V Gan, WJ Lynch, JP Werder, RB Sikder, AA Lane, K Sim, CB Porrello, E Mazzone, SB Sly, PD Steptoe, RJ Spann, KM Sukkar, MB Upham, JW Phipps, S

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Publisher:: Public Library of Science (PLoS)
Publication Type:: Journal Article
Citation:: PLoS pathogens, 2020, 16, (7)
Issue Date:: 2020-07-13

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Field	Value	Language
dc.contributor.author	Loh, Z
dc.contributor.author	Simpson, J
dc.contributor.author	Ullah, A
dc.contributor.author	Zhang, V
dc.contributor.author	Gan, WJ
dc.contributor.author	Lynch, JP
dc.contributor.author	Werder, RB
dc.contributor.author	Sikder, AA
dc.contributor.author	Lane, K
dc.contributor.author	Sim, CB
dc.contributor.author	Porrello, E
dc.contributor.author	Mazzone, SB
dc.contributor.author	Sly, PD
dc.contributor.author	Steptoe, RJ
dc.contributor.author	Spann, KM
dc.contributor.author	Sukkar, MB
dc.contributor.author	Upham, JW
dc.contributor.author	Phipps, S
dc.date.accessioned	2020-09-25T05:18:34Z
dc.date.available	2020-05-24
dc.date.available	2020-09-25T05:18:34Z
dc.date.issued	2020-07-13
dc.identifier.citation	PLoS pathogens, 2020, 16, (7)
dc.identifier.issn	1553-7366
dc.identifier.issn	1553-7374
dc.identifier.uri	http://hdl.handle.net/10453/142862
dc.description.abstract	Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer. Anti-HMGB1 ablated lung ILC2 numbers and ASM growth in vivo, and inhibited ILC2-mediated ASM cell proliferation in a co-culture model. Furthermore, we identified that HMGB1/RAGE (receptor for advanced glycation endproducts) signalling mediates an ILC2-intrinsic IL-13 auto-amplification loop. In summary, therapeutic targeting of the HMGB1/RAGE signalling axis may act as a novel asthma preventative by dampening ILC2-mediated type-2 inflammation and associated ASM remodelling.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Public Library of Science (PLoS)
dc.relation.ispartof	PLoS pathogens
dc.relation.isbasedon	10.1371/journal.ppat.1008651
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0605 Microbiology, 1107 Immunology, 1108 Medical Microbiology
dc.subject.classification	Virology
dc.subject.mesh	Muscle, Smooth
dc.subject.mesh	Lymphocytes
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Inflammation
dc.subject.mesh	HMGB1 Protein
dc.subject.mesh	Airway Remodeling
dc.subject.mesh	Receptor for Advanced Glycation End Products
dc.subject.mesh	Muscle, Smooth
dc.subject.mesh	Lymphocytes
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Inflammation
dc.subject.mesh	HMGB1 Protein
dc.subject.mesh	Airway Remodeling
dc.subject.mesh	Receptor for Advanced Glycation End Products
dc.subject.mesh	Airway Remodeling
dc.subject.mesh	Animals
dc.subject.mesh	HMGB1 Protein
dc.subject.mesh	Inflammation
dc.subject.mesh	Lymphocytes
dc.subject.mesh	Mice
dc.subject.mesh	Muscle, Smooth
dc.subject.mesh	Receptor for Advanced Glycation End Products
dc.title	HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling.
dc.type	Journal Article
utslib.citation.volume	16
utslib.location.activity	United States
utslib.for	0605 Microbiology
utslib.for	1107 Immunology
utslib.for	1108 Medical Microbiology
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Pharmacy
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-09-25T05:18:30Z
pubs.issue	7
pubs.publication-status	Published
pubs.volume	16
utslib.citation.issue	7

Abstract:

Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer. Anti-HMGB1 ablated lung ILC2 numbers and ASM growth in vivo, and inhibited ILC2-mediated ASM cell proliferation in a co-culture model. Furthermore, we identified that HMGB1/RAGE (receptor for advanced glycation endproducts) signalling mediates an ILC2-intrinsic IL-13 auto-amplification loop. In summary, therapeutic targeting of the HMGB1/RAGE signalling axis may act as a novel asthma preventative by dampening ILC2-mediated type-2 inflammation and associated ASM remodelling.

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

http://hdl.handle.net/10453/142862