Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with altered innate effector function

Maria Ferrini, Sophia Carvalho, Yoon Hee Cho, Britten Postma, Lucas Miranda Marques, Kent E Pinkerton, Kevan Roberts, Zeina Jaffar

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma. Methods: Pregnant C57BL/6 mice were exposed to either ETS or filtered air throughout gestation and the effect on pulmonary inflammation in the offspring were examined and compared. Specifically, the effects on eosinophilic inflammation, airway hyperreactivity, goblet cell hyperplasia, properties of pulmonary natural killer (NK) cells and type 2 cytokines elicited in response to inhaled house dust mite (HDM) allergen were investigated in the progeny. Results: Exposure to ETS prenatally significantly exacerbated HDM-induced airway eosinophilic inflammation, hyperreactivity, mucus secretion, cysteinyl leukotriene biosynthesis and type 2 cytokine production in the offspring. Consistently, lung mononuclear cells from ETS-exposed offspring secreted higher levels of IL-13 when stimulated in vitro with anti-αβ TCR antibody or HDM allergen. Moreover, offspring from ETS-exposed dams exhibited a higher frequency of CD11b+ dendritic cells and CD3+CD4+ T lymphocytes in the lungs following allergen inhalation compared to air-exposed mice. Unexpectedly, the exacerbated allergic inflammation in the ETS-exposed offspring was associated with a reduction in CD3-CD19-NK1.1+CD94+ NK cell numbers and their IFN-γ production, highlighting a role for altered innate immunity in the enhanced allergic response. Conclusion: Our results reveal that prenatal exposure to ETS predisposes offspring to an exacerbated allergic airway inflammation that is associated with a reduction in pulmonary NK cell function, suggesting that NK cells play a key role in controlling asthma severity.

Original languageEnglish (US)
Article number30
JournalParticle and Fibre Toxicology
Volume14
Issue number1
DOIs
StatePublished - Aug 22 2017

Fingerprint

Tobacco
Smoke
Inflammation
Environmental Exposure
Natural Killer Cells
Asthma
Lung
Dermatophagoides Antigens
Air
Cytokines
Pyroglyphidae
Goblet Cells
T-cells
Interleukin-13
Biosynthesis
Mucus
Inbred C57BL Mouse
Innate Immunity
Allergens
Dendritic Cells

Keywords

  • Allergic asthma
  • Environmental tobacco smoke
  • Innate immunity
  • Prenatal exposure

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with altered innate effector function. / Ferrini, Maria; Carvalho, Sophia; Cho, Yoon Hee; Postma, Britten; Miranda Marques, Lucas; Pinkerton, Kent E; Roberts, Kevan; Jaffar, Zeina.

In: Particle and Fibre Toxicology, Vol. 14, No. 1, 30, 22.08.2017.

Research output: Contribution to journalArticle

Ferrini, Maria ; Carvalho, Sophia ; Cho, Yoon Hee ; Postma, Britten ; Miranda Marques, Lucas ; Pinkerton, Kent E ; Roberts, Kevan ; Jaffar, Zeina. / Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with altered innate effector function. In: Particle and Fibre Toxicology. 2017 ; Vol. 14, No. 1.
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abstract = "Background: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma. Methods: Pregnant C57BL/6 mice were exposed to either ETS or filtered air throughout gestation and the effect on pulmonary inflammation in the offspring were examined and compared. Specifically, the effects on eosinophilic inflammation, airway hyperreactivity, goblet cell hyperplasia, properties of pulmonary natural killer (NK) cells and type 2 cytokines elicited in response to inhaled house dust mite (HDM) allergen were investigated in the progeny. Results: Exposure to ETS prenatally significantly exacerbated HDM-induced airway eosinophilic inflammation, hyperreactivity, mucus secretion, cysteinyl leukotriene biosynthesis and type 2 cytokine production in the offspring. Consistently, lung mononuclear cells from ETS-exposed offspring secreted higher levels of IL-13 when stimulated in vitro with anti-αβ TCR antibody or HDM allergen. Moreover, offspring from ETS-exposed dams exhibited a higher frequency of CD11b+ dendritic cells and CD3+CD4+ T lymphocytes in the lungs following allergen inhalation compared to air-exposed mice. Unexpectedly, the exacerbated allergic inflammation in the ETS-exposed offspring was associated with a reduction in CD3-CD19-NK1.1+CD94+ NK cell numbers and their IFN-γ production, highlighting a role for altered innate immunity in the enhanced allergic response. Conclusion: Our results reveal that prenatal exposure to ETS predisposes offspring to an exacerbated allergic airway inflammation that is associated with a reduction in pulmonary NK cell function, suggesting that NK cells play a key role in controlling asthma severity.",
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T1 - Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with altered innate effector function

AU - Ferrini, Maria

AU - Carvalho, Sophia

AU - Cho, Yoon Hee

AU - Postma, Britten

AU - Miranda Marques, Lucas

AU - Pinkerton, Kent E

AU - Roberts, Kevan

AU - Jaffar, Zeina

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N2 - Background: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma. Methods: Pregnant C57BL/6 mice were exposed to either ETS or filtered air throughout gestation and the effect on pulmonary inflammation in the offspring were examined and compared. Specifically, the effects on eosinophilic inflammation, airway hyperreactivity, goblet cell hyperplasia, properties of pulmonary natural killer (NK) cells and type 2 cytokines elicited in response to inhaled house dust mite (HDM) allergen were investigated in the progeny. Results: Exposure to ETS prenatally significantly exacerbated HDM-induced airway eosinophilic inflammation, hyperreactivity, mucus secretion, cysteinyl leukotriene biosynthesis and type 2 cytokine production in the offspring. Consistently, lung mononuclear cells from ETS-exposed offspring secreted higher levels of IL-13 when stimulated in vitro with anti-αβ TCR antibody or HDM allergen. Moreover, offspring from ETS-exposed dams exhibited a higher frequency of CD11b+ dendritic cells and CD3+CD4+ T lymphocytes in the lungs following allergen inhalation compared to air-exposed mice. Unexpectedly, the exacerbated allergic inflammation in the ETS-exposed offspring was associated with a reduction in CD3-CD19-NK1.1+CD94+ NK cell numbers and their IFN-γ production, highlighting a role for altered innate immunity in the enhanced allergic response. Conclusion: Our results reveal that prenatal exposure to ETS predisposes offspring to an exacerbated allergic airway inflammation that is associated with a reduction in pulmonary NK cell function, suggesting that NK cells play a key role in controlling asthma severity.

AB - Background: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma. Methods: Pregnant C57BL/6 mice were exposed to either ETS or filtered air throughout gestation and the effect on pulmonary inflammation in the offspring were examined and compared. Specifically, the effects on eosinophilic inflammation, airway hyperreactivity, goblet cell hyperplasia, properties of pulmonary natural killer (NK) cells and type 2 cytokines elicited in response to inhaled house dust mite (HDM) allergen were investigated in the progeny. Results: Exposure to ETS prenatally significantly exacerbated HDM-induced airway eosinophilic inflammation, hyperreactivity, mucus secretion, cysteinyl leukotriene biosynthesis and type 2 cytokine production in the offspring. Consistently, lung mononuclear cells from ETS-exposed offspring secreted higher levels of IL-13 when stimulated in vitro with anti-αβ TCR antibody or HDM allergen. Moreover, offspring from ETS-exposed dams exhibited a higher frequency of CD11b+ dendritic cells and CD3+CD4+ T lymphocytes in the lungs following allergen inhalation compared to air-exposed mice. Unexpectedly, the exacerbated allergic inflammation in the ETS-exposed offspring was associated with a reduction in CD3-CD19-NK1.1+CD94+ NK cell numbers and their IFN-γ production, highlighting a role for altered innate immunity in the enhanced allergic response. Conclusion: Our results reveal that prenatal exposure to ETS predisposes offspring to an exacerbated allergic airway inflammation that is associated with a reduction in pulmonary NK cell function, suggesting that NK cells play a key role in controlling asthma severity.

KW - Allergic asthma

KW - Environmental tobacco smoke

KW - Innate immunity

KW - Prenatal exposure

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