Abstract
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.
Highlights
The prominent role of TH2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can contribute to orchestration of allergic responses
Mice were exposed to doses of diesel exhaust particles (DEPs) and house dust mite (HDM) that elicited almost no inflammatory response on their own to have a model in which we could optimally examine the potential adjuvant capacities of DEPs on HDM-induced airway inflammation
Numbers of dendritic cells (DC), neutrophils, ILC2s, CD41 T cells, CD81 T cells, and eosinophils were significantly increased in the bronchoalveolar lavage fluid (BALF) of WT mice that received combined DEP1HDM compared with those in the 3 control groups (Fig 1, D-I)
Summary
The prominent role of TH2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can contribute to orchestration of allergic responses. Objective: We sought to investigate the relative contribution of ILC2 and adaptive TH2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. As well as inflammation, and intracellular cytokine expression in ILC2s and TH2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Results: Concomitant DEP1HDM 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 DEP1HDMexposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. A crucial role for the adaptive immune system was shown on concomitant DEP1HDM exposure. A crucial role for the adaptive immune system was shown on concomitant DEP1HDM exposure. (J Allergy Clin Immunol 2017;139:246-57.)
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