Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:139

Article

De Grove, Katrien C.¹  Provoost, Sharen¹  Hendriks, Rudi W.²  McKenzie, Andrew N. J.³  Seys, Leen J. M.¹  Kumar, Smitha¹  Maes, Tania¹  Brusselle, Guy G.¹  Joos, Guy F.¹ 

[1] Ghent Univ Hosp, Dept Resp Med, Lab Translat Res Obstruct Pulm Dis, Ghent, Belgium

[2] Erasmus MC, Dept Pulm Med, Rotterdam, Netherlands

[3] MRC, Mol Biol Lab, Francis Crick Ave, Cambridge, England

关键词: Diesel exhaust particles;    house dust mite;    type 2 innate lymphoid cell;    T(H)2 response;    asthma;   

DOI  :  10.1016/j.jaci.2016.03.044

来源: Elsevier

【 摘 要 】

Background: Although the prominent role of T(H)2 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. Objective: We sought to investigate the relative contribution of ILC2 and adaptive T(H)2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Methods: Wild-type, Gata-3 (+/ nlslacZ) (Gata-3-haploinsufficient), RAR-related orphan receptor alpha(ROR alpha) (fl/ fl) IL7R (Cre) (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 T(H)2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Results: Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and T(H)2 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 T(H)2 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. Conclusion: These data indicate that dysregulation of ILC2s and T(H)2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure.

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