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Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses.
J Allergy Clin Immunol 2017; 139(1):246-257.e4JA

Abstract

BACKGROUND

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.

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Authors+Show Affiliations

Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium. Electronic address: sharen.provoost@UGent.be.Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, United Kingdom.Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27315767

Citation

De Grove, Katrien C., et al. "Dysregulation of Type 2 Innate Lymphoid Cells and TH2 Cells Impairs Pollutant-induced Allergic Airway Responses." The Journal of Allergy and Clinical Immunology, vol. 139, no. 1, 2017, pp. 246-257.e4.
De Grove KC, Provoost S, Hendriks RW, et al. Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses. J Allergy Clin Immunol. 2017;139(1):246-257.e4.
De Grove, K. C., Provoost, S., Hendriks, R. W., McKenzie, A. N. J., Seys, L. J. M., Kumar, S., ... Joos, G. F. (2017). Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses. The Journal of Allergy and Clinical Immunology, 139(1), pp. 246-257.e4. doi:10.1016/j.jaci.2016.03.044.
De Grove KC, et al. Dysregulation of Type 2 Innate Lymphoid Cells and TH2 Cells Impairs Pollutant-induced Allergic Airway Responses. J Allergy Clin Immunol. 2017;139(1):246-257.e4. PubMed PMID: 27315767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses. AU - De Grove,Katrien C, AU - Provoost,Sharen, AU - Hendriks,Rudi W, AU - McKenzie,Andrew N J, AU - Seys,Leen J M, AU - Kumar,Smitha, AU - Maes,Tania, AU - Brusselle,Guy G, AU - Joos,Guy F, Y1 - 2016/05/11/ PY - 2015/07/14/received PY - 2016/03/03/revised PY - 2016/03/15/accepted PY - 2016/6/19/pubmed PY - 2017/7/20/medline PY - 2016/6/19/entrez KW - Diesel exhaust particles KW - T(H)2 response KW - asthma KW - house dust mite KW - type 2 innate lymphoid cell SP - 246 EP - 257.e4 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 139 IS - 1 N2 - BACKGROUND: 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. 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/27315767/Dysregulation_of_type_2_innate_lymphoid_cells_and_TH2_cells_impairs_pollutant_induced_allergic_airway_responses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(16)30271-8 DB - PRIME DP - Unbound Medicine ER -