4-Octyl Itaconate Alleviates Airway Eosinophilic Inflammation by Suppressing Chemokines and Eosinophil Development.

Yin, M; Wadhwa, R; Marshall, JE; Gillis, CM; Kim, RY; Dua, K; Palsson-McDermott, EM; Fallon, PG; Hansbro, PM; O'Neill, LAJ

4-Octyl Itaconate Alleviates Airway Eosinophilic Inflammation by Suppressing Chemokines and Eosinophil Development.

Yin, M Wadhwa, R Marshall, JE Gillis, CM Kim, RY Dua, K

Palsson-McDermott, EM Fallon, PG Hansbro, PM O'Neill, LAJ

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Publisher:: AMER ASSOC IMMUNOLOGISTS
Publication Type:: Journal Article
Citation:: J Immunol, 2024, 212, (1), pp. 13-23
Issue Date:: 2024-01-01

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Field	Value	Language
dc.contributor.author	Yin, M
dc.contributor.author	Wadhwa, R
dc.contributor.author	Marshall, JE
dc.contributor.author	Gillis, CM
dc.contributor.author	Kim, RY
dc.contributor.author	Dua, K https://orcid.org/0000-0002-7507-1159
dc.contributor.author	Palsson-McDermott, EM
dc.contributor.author	Fallon, PG
dc.contributor.author	Hansbro, PM
dc.contributor.author	O'Neill, LAJ
dc.date.accessioned	2024-10-08T22:16:12Z
dc.date.available	2023-10-20
dc.date.available	2024-10-08T22:16:12Z
dc.date.issued	2024-01-01
dc.identifier.citation	J Immunol, 2024, 212, (1), pp. 13-23
dc.identifier.issn	0022-1767
dc.identifier.issn	1550-6606
dc.identifier.uri	http://hdl.handle.net/10453/181246
dc.description.abstract	4-Octyl itaconate (4-OI) is a derivative of the Krebs cycle-derived metabolite itaconate and displays an array of antimicrobial and anti-inflammatory properties through modifying cysteine residues within protein targets. We have found that 4-OI significantly reduces the production of eosinophil-targeted chemokines in a variety of cell types, including M1 and M2 macrophages, Th2 cells, and A549 respiratory epithelial cells. Notably, the suppression of these chemokines in M1 macrophages was found to be NRF2-dependent. In addition, 4-OI can interfere with IL-5 signaling and directly affect eosinophil differentiation. In a model of eosinophilic airway inflammation in BALB/c mice, 4-OI alleviated airway resistance and reduced eosinophil recruitment to the lungs. Our findings suggest that itaconate derivatives could be promising therapeutic agents for the treatment of eosinophilic asthma.
dc.format	Print
dc.language	eng
dc.publisher	AMER ASSOC IMMUNOLOGISTS
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation.ispartof	J Immunol
dc.relation.isbasedon	10.4049/jimmunol.2300155
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.classification	3204 Immunology
dc.subject.mesh	Mice
dc.subject.mesh	Animals
dc.subject.mesh	Eosinophils
dc.subject.mesh	Pulmonary Eosinophilia
dc.subject.mesh	Chemokines
dc.subject.mesh	Inflammation
dc.subject.mesh	Eosinophils
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Pulmonary Eosinophilia
dc.subject.mesh	Inflammation
dc.subject.mesh	Chemokines
dc.subject.mesh	Mice
dc.subject.mesh	Animals
dc.subject.mesh	Eosinophils
dc.subject.mesh	Pulmonary Eosinophilia
dc.subject.mesh	Chemokines
dc.subject.mesh	Inflammation
dc.title	4-Octyl Itaconate Alleviates Airway Eosinophilic Inflammation by Suppressing Chemokines and Eosinophil Development.
dc.type	Journal Article
utslib.citation.volume	212
utslib.location.activity	United States
utslib.for	1107 Immunology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Health
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)/Associate Member
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)/Australian Institute for Microbiology & Infection (AIMI) Associate Member
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Research Consortium in Complementary and Integrative Medicine (ARCCIM)
utslib.copyright.status	closed_access	*
dc.date.updated	2024-10-08T22:16:08Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	212
utslib.citation.issue	1

Abstract:

4-Octyl itaconate (4-OI) is a derivative of the Krebs cycle-derived metabolite itaconate and displays an array of antimicrobial and anti-inflammatory properties through modifying cysteine residues within protein targets. We have found that 4-OI significantly reduces the production of eosinophil-targeted chemokines in a variety of cell types, including M1 and M2 macrophages, Th2 cells, and A549 respiratory epithelial cells. Notably, the suppression of these chemokines in M1 macrophages was found to be NRF2-dependent. In addition, 4-OI can interfere with IL-5 signaling and directly affect eosinophil differentiation. In a model of eosinophilic airway inflammation in BALB/c mice, 4-OI alleviated airway resistance and reduced eosinophil recruitment to the lungs. Our findings suggest that itaconate derivatives could be promising therapeutic agents for the treatment of eosinophilic asthma.

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http://hdl.handle.net/10453/181246