Abstract
Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the “immunomodulatory barrier” of the airway epithelium.
To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion.
Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung.
These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.
Footnotes
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Note from the Editors: The term Clara cell is still used in the European Respiratory Journal (ERJ) and in other publications in the field. However, the use and possible replacement of this term has been the subject of some debate, as discussed in the ERJ article “The Clara cell: a “Third Reich eponym”?” by A. Winkelmann and T. Noak (Eur Respir J 2010; 36: 722–727).
Support Statement
This work was supported in part by grants from the Deutsche Forschungsgemeinschaft (Transregio 22, Project A9) and the Stiftung für Pathobiochemie und Molekulare Diagnostik, DGKL.
Statement of Interest
None declared.
- Received December 21, 2011.
- Accepted July 7, 2011.
- ©ERS 2012