• Cristan Herbert, Alexander M Shadie, and Rakesh K Kumar.
• Inflammation and Infection Research, Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, N.S.W., Australia.
• Int. Arch. Allergy Immunol. 2013 Jan 1;162(3):253-62.

BackgroundThe role of Th17 cell-derived cytokines in the pathogenesis of airway inflammation and remodelling in mild asthma remains unclear. We investigated this in a mouse model which reproduces most of the features of the human disease.MethodsSystemically sensitised BALB/c mice were challenged via the airways with a low mass concentration of ovalbumin aerosol for 8 weeks to induce lesions of mild chronic asthma. Changes were compared with those in animals deficient in signalling via the interleukin (IL)-17 receptor A (IL-17R). Low-passage airway epithelial cells (AEC) and fibroblasts were cultured with IL-17A, or with media from Th17-polarised cells, to assess activation.ResultsIn CD4+ T cells from chronically challenged mice, expression of mRNA for Th17 cytokines IL-17A, IL-17F, IL-21 and IL-22 was significantly increased. Both recombinant IL-17A and media from Th17 cells significantly stimulated the production of various pro-inflammatory and pro-remodelling cytokines by AEC and fibroblasts. In the mouse model, abrogation of IL-17R signalling had no effect on the development of airway inflammation or on most changes of remodelling. However, numbers of mucus-producing cells and expression of mRNA for Gob-5 were attenuated in the absence of IL-17R signalling.ConclusionsAlthough IL-17A and Th17 cells stimulate cytokine production by structural cells of the airways, and Th17 cells are induced in our model of mild chronic asthma, signalling via IL-17R did not contribute significantly to the development of airway inflammation and most changes of remodelling in this model. However, in mild asthma, IL-17A appears to have a role in the goblet cell response in the airways.© 2013 S. Karger AG, Basel.

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