Use of mouse models of allergic rhinitis to study the upper and lower airway link.
OBJECTIVE
Allergic rhinitis and asthma are examples of a continuum of airway diseases with diverse clinical manifestations. This review examines the most recent work in mouse models studying upper and lower airway links and interactions.


RESULTS
The concept of united airways has been supported by investigative and epidemiological studies. Studies using mouse models of asthma and models of allergic rhinitis have demonstrated that analogous pathways lead to inflammation and airway hyperresponsiveness. Th2-type T cells and IL-13 play important immunopathologic roles. Recent studies have examined upper airway mucosal immune responses and development of both allergic and tolerant phenotypes. In a model of allergic airways disease, there is evidence of lower airway inflammation and airways hyperresponsiveness following application of allergen only to the nares, suggesting local stimulation can activate distal allergic responses. Immunomodulatory properties of the airway mucosa have also been explored. Allergen-specific tolerance can be induced by appropriate stimulation of airway mucosa and is associated with activation of IL-10-producing T cells. This effect is mediated by antigen presenting cells, especially dendritic cells.


CONCLUSIONS
Immune stimulation of the airway mucosa, both in the upper and lower airways, results in active T-cell-mediated immune responses leading toward tolerance or asthma and allergic rhinitis. Regulation of these T-cell responses is currently under investigation. It is clear from these studies that antigenic stimulation of any part of the respiratory mucosa can have ripple effects along the entire airway and supports the concept of united airways.
McCusker
Christine T
CT
Division of Allergy and Immunology, Montreal Children's Hospital and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada. christine.mccusker@muhc.mcgill.ca
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D012137:Respiratory System / Q000473:pathology*; D012221:Rhinitis, Allergic, Perennial / Q000453:epidemiology / Q000209:etiology*
D000485:Allergens