• Katrien C De Grove, Sharen Provoost, Rudi W Hendriks, McKenzie Andrew N J ANJ MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom., Seys Leen J M LJM Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Smitha Kumar, Tania Maes, Guy G Brusselle, and Guy F Joos.
• Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
• J. Allergy Clin. Immunol. 2017 Jan 1; 139 (1): 246-257.e4.

BackgroundAlthough the prominent role of TH2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known.ObjectiveWe sought to investigate the relative contribution of ILC2 and adaptive TH2 cell responses in a murine model of DEP-enhanced allergic airway inflammation.MethodsWild-type, Gata-3+/nlslacZ (Gata-3-haploinsufficient), RAR-related orphan receptor α (RORα)fl/flIL7RCre (ILC2-deficient), and recombination-activating gene (Rag) 2-/- mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and TH2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed.ResultsConcomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and TH2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and TH2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2-/- mice.ConclusionThese data indicate that dysregulation of ILC2s and TH2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure.Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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