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

Background: Whereas the prominent role of T helper 2 (Th2) cells in type 2 immune responses is well established, also type 2 innate lymphoid cells (ILC2) can contribute to the orchestration of allergic responses. Several studies provided evidence that allergen-induced airway responses can be further enhanced upon exposure to environmental pollutants, such as diesel exhaust particles (DEP). The components and pathways responsible remain however incompletely known. Objective: To investigate the relative contribution of ILC2 and Th2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Methods: Wild-type (WT), Rag2^-/- mice and Gata3^+/nlslacZ mice were challenged with saline, DEP or house dust mite (HDM), or combined DEP+HDM. Airway inflammation and intracellular cytokine expression in ILC2 and Th2 cells were assessed in the bronchoalveolar lavage fluid and lung tissue. Results: Concomitant DEP+HDM exposure significantly enhanced the allergic airway inflammation, characterized by increased IL-33, airway eosinophilia, goblet cell metaplasia, accumulation of ILC2 and Th2 cells and type 2 cytokine production, compared to DEP or HDM. These allergic inflammatory immune responses were abolished in Rag2^-/- mice that received combined DEP+HDM. Moreover, haplo-insufficiency for Gata-3 reduced the number of functional ILC2 and Th2 cells, attenuating DEP-enhanced allergic airway inflammation. Conclusion: These data indicate that dysregulation of ILC2 and Th2 cells attenuates DEP-enhanced allergic airway inflammation. Funding: This project is supported by the IUAP/BELSPO P7/30, FWO-Vlaanderen and Lung Foundation Netherlands (to R.W.H.).