Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells
Burchell, J.T., Wikstrom, M.E., Stumbles, P.A., Sly, P.D. and Turner, D.J. (2009) Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells. AJP: Lung Cellular and Molecular Physiology, 296 (3). L307-L319.
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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 IgG1, 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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Veterinary and Biomedical Sciences|
|Publisher:||American Physiological Society|
|Copyright:||2009 American Physiological Society|
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