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



We sought to investigate the relative contribution of ILC2 and adaptive TH2 cell responses in a murine model of DEP-enhanced allergic airway inflammation.



Wild-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.



Concomitant 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.



These 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.
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
Katrien C
KC
De Grove
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium. Electronic address: sharen.provoost@UGent.be.
Sharen
S
Provoost
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
Rudi W
RW
Hendriks
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.
Andrew N J
ANJ
McKenzie
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
Leen J M
LJM
Seys
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
Smitha
S
Kumar
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
Tania
T
Maes
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
Guy G
GG
Brusselle
Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
Guy F
GF
Joos
D056704:Adaptive Immunity; D000393:Air Pollutants; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005260:Female; D050990:GATA3 Transcription Factor / Q000276:immunology; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052638:Particulate Matter; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001335:Vehicle Emissions
D000393:Air Pollutants; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D052638:Particulate Matter; D001335:Vehicle Emissions
Diesel exhaust particles; T(H)2 response; asthma; house dust mite; type 2 innate lymphoid cell