Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk for persistent airways hyper-responsiveness in experimental asthma

Strickland, D. H., Thomas, J. A., Mok, D., Blank, F., McKenna, K. L., Larcombe, A. N., Sly, P. D. and Holt, P. G. (2012) Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk for persistent airways hyper-responsiveness in experimental asthma. Mucosal Immunology, 5 3: 332-341. doi:10.1038/mi.2012.13

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Author Strickland, D. H.
Thomas, J. A.
Mok, D.
Blank, F.
McKenna, K. L.
Larcombe, A. N.
Sly, P. D.
Holt, P. G.
Title Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk for persistent airways hyper-responsiveness in experimental asthma
Journal name Mucosal Immunology   Check publisher's open access policy
ISSN 1933-0219
1935-3456
Publication date 2012-05
Sub-type Article (original research)
DOI 10.1038/mi.2012.13
Volume 5
Issue 3
Start page 332
End page 341
Total pages 10
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Collection year 2013
Language eng
Formatted abstract
A hallmark of atopic asthma is development of chronic airways hyper-responsiveness (AHR) that persists in the face of ongoing exposure to perennial aeroallergens. We investigated underlying mechanisms in sensitized rats focusing on a strain expressing the high-allergen – responder phenotype characteristic of human atopic asthmatics, and find that their high susceptibility to aeroallergen-induced persistent AHR is associated with deficiencies in the immunoregulatory and mucosal trafficking properties of inducible T-regulatory cells (iTregs). Counterintuitively, AHR susceptibility was inversely related to aeroallergen exposure level, high exposures conferring protection. We demonstrate that underlying this AHR-susceptible phenotype is reduced capacity of airway mucosal dendritic cells (AMDCs) for allergen sampling in vivo ; this defect is microenvironmentally acquired, as allergen uptake by these cells in vitro is normal. Moreover, intranasal transfer of in vitro aeroallergen-loaded AMDC from na ï ve animals into AHR-susceptible animals during prolonged aerosol challenge markedly boosts subsequent accumulation of iTregs in the airway mucosa and rapidly resolves their chronic AHR, suggesting that compromised antigen surveillance by AMDC resulting in defective functional programming of iTreg may be causally related to AHR susceptibility.
Keyword Regulatory T-cells
Chemokine receptors Ccr4
Dust mite allergen
Respiratory tract
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
Official 2013 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 12 times in Scopus Article | Citations
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