Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells

Burchell, Jennifer T., Wikstrom, Matthew E., Stumbles, Philip A., Sly, Peter D. and Turner, Debra J. (2009) Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells. American Journal of Physiology - Lung Cellular and Molecular Physiology, 296 3: L307-L319. doi:10.1152/ajplung.00521.2007


Author Burchell, Jennifer T.
Wikstrom, Matthew E.
Stumbles, Philip A.
Sly, Peter D.
Turner, Debra J.
Title Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells
Journal name American Journal of Physiology - Lung Cellular and Molecular Physiology   Check publisher's open access policy
ISSN 1040-0605
1522-1504
Publication date 2009-03
Sub-type Article (original research)
DOI 10.1152/ajplung.00521.2007
Volume 296
Issue 3
Start page L307
End page L319
Total pages 13
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Language eng
Abstract Understanding the mechanisms involved in respiratory tolerance to inhaled allergens could potentially result in improved therapies for asthma and allergic diseases. Airway hyperresponsiveness (AHR) is a major feature of allergic asthma, thus the aim of the current study was to investigate mechanisms underlying suppression of allergen-induced AHR during chronic allergen exposure. Adult BALB/c mice were systemically sensitized with ovalbumin (OVA) in adjuvant and then challenged with a single 3 or 6 wk of OVA aerosols. Airway and parenchymal responses to inhaled methacholine (MCh), inflammatory cell counts, cytokines, OVA-specific IgE and IgG1, parenchymal histology, and numbers of airway CD4+69+ activated and CD4+25 +FoxP3+ regulatory T (Treg) cells were assessed 24 h after the final aerosol. Single OVA challenge resulted in AHR, eosinophilia, increased serum OVA-specific IgE, and T helper 2 (Th2) cytokines in bronchoalveolar lavage (BAL) but no difference in numbers of Treg compared with control mice. Three weeks of OVA challenges resulted in suppression of AHR and greater numbers of airway Treg cells and increased transforming growth factor-β1 (TGFβ1) compared with control mice despite the presence of increased eosinophilia, OVA-specific IgE and IgG 1, and airway remodeling. Six weeks of OVA challenges restored AHR, whereas airway Treg numbers, TGFβ1, BAL eosinophilia, and Th2 cytokines returned to control levels. Partial in vivo depletion or adoptive transfer of Treg cells restored or inhibited AHR, respectively, but did not affect TGFβ1 or Th2 cytokine production. In conclusion, AHR suppression is mediated by airway Treg cells and potentially via a paracrine induction of TGFβ1 in the airways.
Keyword asthma
T regulatory cell
lung function
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Faculty of Health and Behavioural Sciences -- Publications
 
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Created: Wed, 17 Nov 2010, 11:19:54 EST