Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice - 05/02/16
, Angela Haczku, MD, PhD c, d, ∗⁎ 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.
Le texte complet de cet article est disponible en PDF.Key words : Ozone, group 2 innate lymphoid cells, airway hyperresponsiveness
Abbreviations used : AHR, BAL, FACS, ILC2, O3, 18O3, qPCR
Plan
| Supported by grant R01AI072197 (to A.H.), RC1ES018505 (to A.H.), P30ES013508 (to A.H.), R21 AI059621 (to A.B. and A.H.), and AI098428 (to A.B.). |
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| Disclosure of potential conflict of interest: Q. Yang and A. Bhandoola have received research support from the National Institutes of Health (NIH; grants R21 AI059621 to A.B. and A.H. and AI098428 to A.B., NIH intramural funding). M. Q. Ge, B. Kokalari, I. G. Redai, X. Wang, and A. Haczku have received research support from the NIH (grants R01AI072197 to A.H.; RC1ES018505 to A.H.; P30ES013508 to A.H.; and R21 AI059621 to A.B. and A.H.). D. M. Kemeny has received research support from the NMRC/1321/2012; and has received consultancy fees from Johnson & Johnson as a member of the advisory committee on adverse reactions to erythropoietin. |
Vol 137 - N° 2
P. 571-578 - février 2016 Retour au numéro
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