17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      abstract
      1 , , 1 , 2 , 3 , 3 , 3 , 1
      Journal of Inflammation (London, England)
      BioMed Central
      2nd Cross Company Respiratory Symposium
      6-7 September 2012

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Conference
          J Inflamm (Lond)
          J Inflamm (Lond)
          Journal of Inflammation (London, England)
          BioMed Central
          1476-9255
          2013
          14 August 2013
          : 10
          : Suppl 1
          : P3
          Affiliations
          [1 ]Inflammation and Remodeling, Pfizer, Cambridge, Massachusetts, 02140, USA
          [2 ]Drug Safety R&D, Pfizer, Cambridge, Massachusetts, 02140, USA
          [3 ]Immunoscience, Pfizer, Cambridge, Massachusetts, 02140, USA
          Article
          1476-9255-10-S1-P3
          10.1186/1476-9255-10-S1-P3
          3750935
          df9e22ee-596a-440d-aab9-367a0ce9be14
          Copyright © 2013 Hubeau et al; licensee 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.

          2nd Cross Company Respiratory Symposium
          Horsham, UK
          6-7 September 2012
          History
          Categories
          Poster Presentation

          Immunology
          Immunology

          Comments

          Comment on this article