The Duffy antigen receptor for chemokines regulates asthma pathophysiology

Chapman, DG; Mougey, EB; Van der Velden, JL; Lahue, KG; Aliyeva, M; Daphtary, N; George, KL; Hoffman, SM; Schneider, RW; Tracy, RP; Worthen, GS; Poynter, ME; Peters, SP; Lima, JJ; Janssen-Heininger, YMW; Irvin, CG

The Duffy antigen receptor for chemokines regulates asthma pathophysiology

Mougey, EB Van der Velden, JL Lahue, KG Aliyeva, M Daphtary, N George, KL Hoffman, SM Schneider, RW Tracy, RP Worthen, GS Poynter, ME Peters, SP Lima, JJ Janssen-Heininger, YMW Irvin, CG

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Publication Type:: Journal Article
Citation:: Clinical and Experimental Allergy, 2017, 47 (9), pp. 1214 - 1222
Issue Date:: 2017-09-01

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Field	Value	Language
dc.contributor.author	Chapman, DG https://orcid.org/0000-0002-8211-1817	en_US
dc.contributor.author	Mougey, EB	en_US
dc.contributor.author	Van der Velden, JL	en_US
dc.contributor.author	Lahue, KG	en_US
dc.contributor.author	Aliyeva, M	en_US
dc.contributor.author	Daphtary, N	en_US
dc.contributor.author	George, KL	en_US
dc.contributor.author	Hoffman, SM	en_US
dc.contributor.author	Schneider, RW	en_US
dc.contributor.author	Tracy, RP	en_US
dc.contributor.author	Worthen, GS	en_US
dc.contributor.author	Poynter, ME	en_US
dc.contributor.author	Peters, SP	en_US
dc.contributor.author	Lima, JJ	en_US
dc.contributor.author	Janssen-Heininger, YMW	en_US
dc.contributor.author	Irvin, CG	en_US
dc.date.available	2017-03-27	en_US
dc.date.issued	2017-09-01	en_US
dc.identifier.citation	Clinical and Experimental Allergy, 2017, 47 (9), pp. 1214 - 1222	en_US
dc.identifier.issn	0954-7894	en_US
dc.identifier.uri	http://hdl.handle.net/10453/125193
dc.description.abstract	© 2017 John Wiley & Sons Ltd Background: The Duffy antigen receptor for chemokines (DARC) is an atypical receptor that regulates pro-inflammatory cytokines. However, the role of DARC in asthma pathophysiology is unknown. Objective: To determine the role of DARC in allergic airways disease in mice, and the association between DARC single nucleotide polymorphisms (SNPs) and clinical outcomes in patients with asthma. Methods: Mice with targeted disruption of the Darc gene (Darc∆E2) or WT mice were challenged over 3 weeks with house dust mite (HDM) antigen. Allergic airways disease was assessed 24 hours and 7 days following the final challenge. Additionally, associations between DARC SNPs and clinical outcomes were analysed in a cohort of poorly controlled asthmatics. Results: Total airway inflammation following HDM did not differ between Darc∆E2 and WT mice. At 24 hours, Darc∆E2 mice had increased airway hyperresponsiveness; however, at 7 days airway hyperresponsiveness had completely resolved in Darc∆E2 but persisted in WT mice. In poorly controlled asthmatics, DARC SNPs were associated with worse asthma control at randomization and subsequent increased risk of healthcare utilization (odds ratio 3.13(1.37-7.27), P=.0062). Conclusions and Clinical Relevance: Our animal model and human patient data suggest a novel role for DARC in the temporal regulation in asthma pathophysiology and symptoms.	en_US
dc.relation.ispartof	Clinical and Experimental Allergy	en_US
dc.relation.isbasedon	10.1111/cea.12949	en_US
dc.subject.classification	Allergy	en_US
dc.subject.mesh	Respiratory Mucosa	en_US
dc.subject.mesh	Leukocytes	en_US
dc.subject.mesh	Neutrophils	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Respiratory Hypersensitivity	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Disease Susceptibility	en_US
dc.subject.mesh	Receptors, Cell Surface	en_US
dc.subject.mesh	Chemokines	en_US
dc.subject.mesh	Antigens, Dermatophagoides	en_US
dc.subject.mesh	Duffy Blood-Group System	en_US
dc.subject.mesh	Prognosis	en_US
dc.subject.mesh	Severity of Illness Index	en_US
dc.subject.mesh	Gene Expression	en_US
dc.subject.mesh	Phenotype	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Patient Acceptance of Health Care	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Genetic Loci	en_US
dc.subject.mesh	Patient Outcome Assessment	en_US
dc.title	The Duffy antigen receptor for chemokines regulates asthma pathophysiology	en_US
dc.type	Journal Article
utslib.citation.volume	9	en_US
utslib.citation.volume	47	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1117 Public Health and Health Services	en_US
utslib.for	1111 Nutrition and Dietetics	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	9	en_US
pubs.publication-status	Published	en_US
pubs.volume	47	en_US

Abstract:

© 2017 John Wiley & Sons Ltd Background: The Duffy antigen receptor for chemokines (DARC) is an atypical receptor that regulates pro-inflammatory cytokines. However, the role of DARC in asthma pathophysiology is unknown. Objective: To determine the role of DARC in allergic airways disease in mice, and the association between DARC single nucleotide polymorphisms (SNPs) and clinical outcomes in patients with asthma. Methods: Mice with targeted disruption of the Darc gene (Darc∆E2) or WT mice were challenged over 3 weeks with house dust mite (HDM) antigen. Allergic airways disease was assessed 24 hours and 7 days following the final challenge. Additionally, associations between DARC SNPs and clinical outcomes were analysed in a cohort of poorly controlled asthmatics. Results: Total airway inflammation following HDM did not differ between Darc∆E2 and WT mice. At 24 hours, Darc∆E2 mice had increased airway hyperresponsiveness; however, at 7 days airway hyperresponsiveness had completely resolved in Darc∆E2 but persisted in WT mice. In poorly controlled asthmatics, DARC SNPs were associated with worse asthma control at randomization and subsequent increased risk of healthcare utilization (odds ratio 3.13(1.37-7.27), P=.0062). Conclusions and Clinical Relevance: Our animal model and human patient data suggest a novel role for DARC in the temporal regulation in asthma pathophysiology and symptoms.

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

http://hdl.handle.net/10453/125193