Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice

Qi Yang, Moyar Q. Ge, Blerina Kokalari, Imre G. Redai, Xinxin Wang, David M. Kemeny, Avinash Bhandoola, Angela Franciska Haczku

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background Asthmatic patients are highly susceptible to air pollution and in particular to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. Objective Using mouse models of O3-induced airway inflammation and airway hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2s). Methods C57BL/6 and BALB/c mice were exposed to Aspergillus fumigatus, O3, or both (3 ppm for 2 hours). ILC2s were isolated by means of fluorescence-activated cell sorting and studied for Il5 and Il13 mRNA expression. ILC2s were depleted with anti-Thy1.2 mAb and replaced by means of intratracheal transfer of ex vivo expanded Thy1.1 ILC2s. Cytokine levels (ELISA and quantitative PCR), inflammatory cell profile, and AHR (flexiVent) were assessed in the mice. Results In addition to neutrophil influx, O3 inhalation elicited the appearance of eosinophils and IL-5 in the airways of BALB/c but not C57BL/6 mice. Although O3-induced expression of IL-33, a known activator of ILC2s, in the lung was similar between these strains, isolated pulmonary ILC2s from O3-exposed BALB/c mice had significantly greater Il5 and Il13 mRNA expression than C57BL/6 mice. This suggested that an altered ILC2 function in BALB/c mice might mediate the increased O3 responsiveness. Indeed, anti-Thy1.2 treatment abolished but ILC2s added back dramatically enhanced O3-induced AHR. Conclusions O3-induced activation of pulmonary ILC2s was necessary and sufficient to mediate asthma-like changes in BALB/c mice. This previously unrecognized role of ILC2s might help explain the heightened susceptibility of human asthmatic airways to O3 exposure.

Original languageEnglish (US)
Pages (from-to)571-578
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume137
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Ozone
Lymphocytes
Inflammation
Interleukin-13
Inbred C57BL Mouse
Lung
Inhalation
Messenger RNA
Aspergillus fumigatus
Interleukin-5
Air Pollution
Eosinophils
Flow Cytometry
Neutrophils
Asthma
Enzyme-Linked Immunosorbent Assay
Cytokines
Polymerase Chain Reaction

Keywords

  • airway hyperresponsiveness
  • group 2 innate lymphoid cells
  • Ozone

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice. / Yang, Qi; Ge, Moyar Q.; Kokalari, Blerina; Redai, Imre G.; Wang, Xinxin; Kemeny, David M.; Bhandoola, Avinash; Haczku, Angela Franciska.

In: Journal of Allergy and Clinical Immunology, Vol. 137, No. 2, 01.02.2016, p. 571-578.

Research output: Contribution to journalArticle

Yang, Qi ; Ge, Moyar Q. ; Kokalari, Blerina ; Redai, Imre G. ; Wang, Xinxin ; Kemeny, David M. ; Bhandoola, Avinash ; Haczku, Angela Franciska. / Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice. In: Journal of Allergy and Clinical Immunology. 2016 ; Vol. 137, No. 2. pp. 571-578.
@article{c70411183ea1446a89de01f6b54ef69c,
title = "Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice",
abstract = "Background Asthmatic patients are highly susceptible to air pollution and in particular to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. Objective Using mouse models of O3-induced airway inflammation and airway hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2s). Methods C57BL/6 and BALB/c mice were exposed to Aspergillus fumigatus, O3, or both (3 ppm for 2 hours). ILC2s were isolated by means of fluorescence-activated cell sorting and studied for Il5 and Il13 mRNA expression. ILC2s were depleted with anti-Thy1.2 mAb and replaced by means of intratracheal transfer of ex vivo expanded Thy1.1 ILC2s. Cytokine levels (ELISA and quantitative PCR), inflammatory cell profile, and AHR (flexiVent) were assessed in the mice. Results In addition to neutrophil influx, O3 inhalation elicited the appearance of eosinophils and IL-5 in the airways of BALB/c but not C57BL/6 mice. Although O3-induced expression of IL-33, a known activator of ILC2s, in the lung was similar between these strains, isolated pulmonary ILC2s from O3-exposed BALB/c mice had significantly greater Il5 and Il13 mRNA expression than C57BL/6 mice. This suggested that an altered ILC2 function in BALB/c mice might mediate the increased O3 responsiveness. Indeed, anti-Thy1.2 treatment abolished but ILC2s added back dramatically enhanced O3-induced AHR. Conclusions O3-induced activation of pulmonary ILC2s was necessary and sufficient to mediate asthma-like changes in BALB/c mice. This previously unrecognized role of ILC2s might help explain the heightened susceptibility of human asthmatic airways to O3 exposure.",
keywords = "airway hyperresponsiveness, group 2 innate lymphoid cells, Ozone",
author = "Qi Yang and Ge, {Moyar Q.} and Blerina Kokalari and Redai, {Imre G.} and Xinxin Wang and Kemeny, {David M.} and Avinash Bhandoola and Haczku, {Angela Franciska}",
year = "2016",
month = "2",
day = "1",
doi = "10.1016/j.jaci.2015.06.037",
language = "English (US)",
volume = "137",
pages = "571--578",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice

AU - Yang, Qi

AU - Ge, Moyar Q.

AU - Kokalari, Blerina

AU - Redai, Imre G.

AU - Wang, Xinxin

AU - Kemeny, David M.

AU - Bhandoola, Avinash

AU - Haczku, Angela Franciska

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background Asthmatic patients are highly susceptible to air pollution and in particular to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. Objective Using mouse models of O3-induced airway inflammation and airway hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2s). Methods C57BL/6 and BALB/c mice were exposed to Aspergillus fumigatus, O3, or both (3 ppm for 2 hours). ILC2s were isolated by means of fluorescence-activated cell sorting and studied for Il5 and Il13 mRNA expression. ILC2s were depleted with anti-Thy1.2 mAb and replaced by means of intratracheal transfer of ex vivo expanded Thy1.1 ILC2s. Cytokine levels (ELISA and quantitative PCR), inflammatory cell profile, and AHR (flexiVent) were assessed in the mice. Results In addition to neutrophil influx, O3 inhalation elicited the appearance of eosinophils and IL-5 in the airways of BALB/c but not C57BL/6 mice. Although O3-induced expression of IL-33, a known activator of ILC2s, in the lung was similar between these strains, isolated pulmonary ILC2s from O3-exposed BALB/c mice had significantly greater Il5 and Il13 mRNA expression than C57BL/6 mice. This suggested that an altered ILC2 function in BALB/c mice might mediate the increased O3 responsiveness. Indeed, anti-Thy1.2 treatment abolished but ILC2s added back dramatically enhanced O3-induced AHR. Conclusions O3-induced activation of pulmonary ILC2s was necessary and sufficient to mediate asthma-like changes in BALB/c mice. This previously unrecognized role of ILC2s might help explain the heightened susceptibility of human asthmatic airways to O3 exposure.

AB - Background Asthmatic patients are highly susceptible to air pollution and in particular to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. Objective Using mouse models of O3-induced airway inflammation and airway hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2s). Methods C57BL/6 and BALB/c mice were exposed to Aspergillus fumigatus, O3, or both (3 ppm for 2 hours). ILC2s were isolated by means of fluorescence-activated cell sorting and studied for Il5 and Il13 mRNA expression. ILC2s were depleted with anti-Thy1.2 mAb and replaced by means of intratracheal transfer of ex vivo expanded Thy1.1 ILC2s. Cytokine levels (ELISA and quantitative PCR), inflammatory cell profile, and AHR (flexiVent) were assessed in the mice. Results In addition to neutrophil influx, O3 inhalation elicited the appearance of eosinophils and IL-5 in the airways of BALB/c but not C57BL/6 mice. Although O3-induced expression of IL-33, a known activator of ILC2s, in the lung was similar between these strains, isolated pulmonary ILC2s from O3-exposed BALB/c mice had significantly greater Il5 and Il13 mRNA expression than C57BL/6 mice. This suggested that an altered ILC2 function in BALB/c mice might mediate the increased O3 responsiveness. Indeed, anti-Thy1.2 treatment abolished but ILC2s added back dramatically enhanced O3-induced AHR. Conclusions O3-induced activation of pulmonary ILC2s was necessary and sufficient to mediate asthma-like changes in BALB/c mice. This previously unrecognized role of ILC2s might help explain the heightened susceptibility of human asthmatic airways to O3 exposure.

KW - airway hyperresponsiveness

KW - group 2 innate lymphoid cells

KW - Ozone

UR - http://www.scopus.com/inward/record.url?scp=84957937778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957937778&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2015.06.037

DO - 10.1016/j.jaci.2015.06.037

M3 - Article

C2 - 26282284

AN - SCOPUS:84957937778

VL - 137

SP - 571

EP - 578

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 2

ER -