Research ArticleAsthma

Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation

Science Translational Medicine  05 Oct 2016:
Vol. 8, Issue 359, pp. 359ra132
DOI: 10.1126/scitranslmed.aag1370

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Advanced analysis of asthma

Not all individuals who have respiratory reactions to allergens progress to asthma. In this issue, Cho et al. found that although allergic asthmatics and allergic nonasthmatics both experienced inflammation after allergen challenge, asthmatics had more mucin and type 2 cytokines, and allergen-specific T cells sampled from the airspace had increased innate type 2 receptors. Using orientation-resolved optical coherence tomography, described by Adams et al., they demonstrated that allergic asthmatics also had increased airway smooth muscle mass. This technique allows for in vivo imaging of airway smooth muscle structure and function, which could shed light on the pathogenesis of many respiratory diseases.

Abstract

Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. We used segmental allergen challenge of allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine whether there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4+ T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin, and increased mucin MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC subjects, suggesting differences in the airway epithelial response to inflammation. Finally, AA subjects had increased airway smooth muscle mass at baseline measured in vivo using novel orientation-resolved optical coherence tomography. Our data demonstrate that the development of allergic asthma is dependent on the responsiveness of allergen-specific CD4+ T cells to innate type 2 mediators as well as increased sensitivity of airway epithelial cells and smooth muscle to type 2 inflammation.

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