Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses
- Author
- Katrien De Grove (UGent) , Sharen Provoost (UGent) , Rudi W Hendriks, Andrew NJ McKenzie, Leen Seys (UGent) , Smitha Kumar (UGent) , Tania Maes (UGent) , Guy Brusselle (UGent) and Guy Joos (UGent)
- Organization
- Abstract
- 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.
- Keywords
- Diesel exhaust particles, type 2 innate, lymphoid cell, house dust mite, asthma, TH2 response, THYMIC STROMAL LYMPHOPOIETIN, DIESEL EXHAUST PARTICLES, HOUSE-DUST MITE, ADAPTIVE IMMUNITY, T-CELLS, IN-VIVO, ASTHMA, INFLAMMATION, IL-25, MICE
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8134621
- MLA
- De Grove, Katrien, et al. “Dysregulation of Type 2 Innate Lymphoid Cells and TH2 Cells Impairs Pollutant-Induced Allergic Airway Responses.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 139, no. 1, 2017, pp. 246–57, doi:10.1016/j.jaci.2016.03.044.
- APA
- De Grove, K., Provoost, S., Hendriks, R. W., McKenzie, A. N., Seys, L., Kumar, S., … Joos, G. (2017). Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 139(1), 246–257. https://doi.org/10.1016/j.jaci.2016.03.044
- Chicago author-date
- De Grove, Katrien, Sharen Provoost, Rudi W Hendriks, Andrew NJ McKenzie, Leen Seys, Smitha Kumar, Tania Maes, Guy Brusselle, and Guy Joos. 2017. “Dysregulation of Type 2 Innate Lymphoid Cells and TH2 Cells Impairs Pollutant-Induced Allergic Airway Responses.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 139 (1): 246–57. https://doi.org/10.1016/j.jaci.2016.03.044.
- Chicago author-date (all authors)
- De Grove, Katrien, Sharen Provoost, Rudi W Hendriks, Andrew NJ McKenzie, Leen Seys, Smitha Kumar, Tania Maes, Guy Brusselle, and Guy Joos. 2017. “Dysregulation of Type 2 Innate Lymphoid Cells and TH2 Cells Impairs Pollutant-Induced Allergic Airway Responses.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 139 (1): 246–257. doi:10.1016/j.jaci.2016.03.044.
- Vancouver
- 1.De Grove K, Provoost S, Hendriks RW, McKenzie AN, Seys L, Kumar S, et al. Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2017;139(1):246–57.
- IEEE
- [1]K. De Grove et al., “Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses,” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 139, no. 1, pp. 246–257, 2017.
@article{8134621, abstract = {{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.}}, author = {{De Grove, Katrien and Provoost, Sharen and Hendriks, Rudi W and McKenzie, Andrew NJ and Seys, Leen and Kumar, Smitha and Maes, Tania and Brusselle, Guy and Joos, Guy}}, issn = {{0091-6749}}, journal = {{JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}}, keywords = {{Diesel exhaust particles,type 2 innate,lymphoid cell,house dust mite,asthma,TH2 response,THYMIC STROMAL LYMPHOPOIETIN,DIESEL EXHAUST PARTICLES,HOUSE-DUST MITE,ADAPTIVE IMMUNITY,T-CELLS,IN-VIVO,ASTHMA,INFLAMMATION,IL-25,MICE}}, language = {{eng}}, number = {{1}}, pages = {{246--257}}, title = {{Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses}}, url = {{http://doi.org/10.1016/j.jaci.2016.03.044}}, volume = {{139}}, year = {{2017}}, }
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