Dysregulation of type 2 innate lymphoid cells and Th2 cells impairs pollutant-induced allergic airway responses

Publication date: Available online 11 May 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Katrien C. De Grove, Sharen Provoost, Rudi W. Hendriks, Andrew N.J. McKenzie, Leen J.M. Seys, Smitha Kumar, Tania Maes, Guy G. Brusselle, Guy F. Joos
BackgroundWhereas the prominent role of T helper 2 (Th2) cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2) can also contribute to the orchestration of allergic responses. Several experimental and epidemiological studies have provided evidence that allergen-induced airway responses can be further enhanced upon exposure to environmental pollutants, such as diesel exhaust particles (DEP). However, the components and pathways responsible remain incompletely known.ObjectiveTo investigate the relative contribution of ILC2 and adaptive Th2 cell responses in a murine model of DEP-enhanced allergic airway inflammation.MethodsWild-type (WT), Gata3^+/nlslacZ (Gata-3 haploinsufficient), RORα^fl/flIL7R^Cre (ILC2-deficient) and Rag2^-/- mice were challenged with saline, DEP or house dust mite (HDM), or combined DEP+HDM. Airway hyperresponsiveness as well as inflammation and intracellular cytokine expression in ILC2 and Th2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed.ResultsConcomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2 and Th2 cells, type 2 cytokine production and airway hyperresponsiveness, compared to sole DEP or HDM. Reduced Gata-3 expression decreased the number of functional ILC2 and Th2 cells in DEP+HDM exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, whereas 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 ILC2 and Th2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown upon concomitant DEP+HDM exposure.

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