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Modulation of IL-17A and TL1A largely abrogates house dust mite-induced lung inflammation in murine model of allergic airway disease

Recent studies suggest a role for Th17 responses in the increased airway neutrophilia associated with severe asthma. House dust mite (HDM) is a natural allergen to which asthmatics are often sensitized. Mice repeatedly challenged with HDM extract developed robust airway neutrophilia rapidly evolving into asthma-like disease with increased numbers of eosinophils and lymphocytes in bronchoalveolar lavages (BAL) as well as inflammatory infiltrates, vascular/muscular hypertrophy, interstitial fibrosis, epithelial hyperplasia and mucus accumulation in lung tissues. RNA and protein screening revealed a robust Th17 component post-HDM exposure. We thus evaluated whether IL-17A deficiency could modulate HDM-induced allergic airway disease. Airway neutrophilia was indeed abrogated in IL-17A deficient mice weekly challenged with HDM (acute model), however total BAL cellularity and lung mechanics remained comparable to those of HDM-challenged WT mice. In contrast, IL-17A deficient mice daily exposed to HDM (chronic model) had decreased BAL cellularity associated with reduced numbers of BAL macrophages, neutrophils, eosinophils and lymphocytes. Interestingly antibody neutralization of TL1A, a member of the TNF superfamily known to promote Th2 and Th17 responses, reduced BAL cellularity to baseline levels in HDM-challenged WT mice. Our results thus indicate that targeting Th17 responses can alleviate HDM-induced airway neutrophilia, and can also broadly modulate allergic airway disease.

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Correspondence to C Hubeau.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Hubeau, C., Kubera, J., Hammerman, K. et al. Modulation of IL-17A and TL1A largely abrogates house dust mite-induced lung inflammation in murine model of allergic airway disease. J Inflamm 10, P3 (2013). https://doi.org/10.1186/1476-9255-10-S1-P3

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Keywords

  • Th17 Response
  • House Dust
  • Lung Inflammation
  • House Dust Mite
  • Lung Mechanic