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

Abstract

Background 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. Objective 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). Methods 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. 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 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. Conclusions 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.

Mechanisms and treatments for severe, steroid‐resistant allergic airway disease and asthma

“…demonstrated that the intratracheal instillation of particulate matter resulted in the death of alveolar macrophages and release of IL‐1α, which mediated the development of type 2 responses and allergic sensitization upon subsequent exposure to allergens. Furthermore, the induction of TSLP and IL‐33 by components of air pollution may also augment the function of ILCs that are important in allergic airway sensitization …”

miR-146a Mimics Attenuate Allergic Airway Inflammation by Impacted Group 2 Innate Lymphoid Cells in an Ovalbumin-Induced Asthma Mouse Model

“…ILC2s are abundant in the liver, lungs, skin, and gut [10]. Characteristic surface markers and receptors for chemokines, which are involved in the distribution of lymphoid cells to specific organ sites, are expressed by ILC2s [11]. Two transcription factors, RORα and GATA3, which are stimulated by IL-7, are required for the development of ILC2s [12].…”

Type two innate lymphoid cells: the Janus cells in health and disease

“…In addition to allergens, ambient air pollutants such as ozone can also cause asthma. ILC2s have been shown to mediate ozone‐induce AHR and airway inflammation . In this allergen‐independent asthma, both eosinophils and neutrophils are increased in the lungs and there is evidence that both ILC2s and γδ T cells are involved .…”

“…ILC2s have been shown to mediate ozone‐induce AHR and airway inflammation . In this allergen‐independent asthma, both eosinophils and neutrophils are increased in the lungs and there is evidence that both ILC2s and γδ T cells are involved . Interestingly, there has been a strain difference in ozone sensitivity with BALC/c being more sensitive than B6 .…”