Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice.
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.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pa; T-Cell Biology and Development Section, Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, Md.
Qi
Q
Yang
Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pa; Translational Lung Biology Center, Pulmonary, Critical Care & Sleep Medicine, University of California, Davis, Calif; Department of Microbiology, National University of Singapore, Singapore.
Moyar Q
MQ
Ge
Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pa.
Blerina
B
Kokalari
Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pa.
Imre G
IG
Redai
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pa.
Xinxin
X
Wang
Department of Microbiology, National University of Singapore, Singapore.
David M
DM
Kemeny
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pa; T-Cell Biology and Development Section, Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, Md. Electronic address: avinash.bhandoola@nih.gov.
Avinash
A
Bhandoola
Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pa; Translational Lung Biology Center, Pulmonary, Critical Care & Sleep Medicine, University of California, Davis, Calif. Electronic address: haczku@ucdavis.edu.
Angela
A
Haczku
D000485:Allergens / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004781:Environmental Exposure / Q000009:adverse effects; D004802:Eosinophilia / Q000209:etiology; D007113:Immunity, Innate; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000009:adverse effects*; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D000485:Allergens; D016207:Cytokines; D010126:Ozone
Ozone; airway hyperresponsiveness; group 2 innate lymphoid cells