Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice.
Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice.
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DOI：
10.1016/j.jaci.2015.06.037
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Haczku A
中科院分区：
文献类型：
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作者：
Yang Q;Ge MQ;Kokalari B;Redai IG;Wang X;Kemeny DM;Bhandoola A;Haczku A
Patients with asthma are highly susceptible to air pollution and in particular, to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. Using mouse models of O3-induced airway inflammation and hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2). C57BL/6 and Balb/c mice were exposed to Aspergillus fumigatus and/or O3 (2ppm, 2h). ILC2 were isolated by FACS sorting and studied for IL-5 and IL-13 mRNA expression. ILC2 were depleted with anti-Thy1.2 mAb and replaced by intratracheal transfer of ex vivo expanded Thy1.1 ILC2. Cytokines (ELISA, qPCR), inflammatory cell profile and AHR (FlexiVent) were assessed in the mice. 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 ILC2 in the lung was similar between these strains, isolated pulmonary ILC2 from O3 exposed Balb/c mice had significantly greater IL-5 and IL-13 mRNA expression than those of C57BL/6 mice. This suggested that an altered ILC2 function in Balb/c mice may mediate the increased O3 responsiveness. Indeed, anti-Thy1.2 treatment abolished, whereas ILC2 add-back dramatically enhanced O3-induced AHR. O3-induced activation of pulmonary ILC2 was necessary and sufficient to mediate asthma-like changes in Balb/c mice. This previously unrecognized role of ILC2 may help explain the heightened susceptibility of human asthmatic airways to O3 exposure.
