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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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Please use this url to cite or link to this publication:

Chicago
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.
APA
De Grove, K., Provoost, S., Hendriks, R. W., McKenzie, A. N., Seys, L., Kumar, S., Maes, T., et al. (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.
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.
MLA
De Grove, Katrien, Sharen Provoost, Rudi W Hendriks, et al. “Dysregulation of Type 2 Innate Lymphoid Cells and TH2 Cells Impairs Pollutant-induced Allergic Airway Responses.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 139.1 (2017): 246–257. Print.
@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},
  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://dx.doi.org/10.1016/j.jaci.2016.03.044},
  volume       = {139},
  year         = {2017},
}

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