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

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)
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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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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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