AIM2 participates in house dust mite (HDM)-induced epithelial dysfunctions and ovalbumin (OVA)-induced allergic asthma in infant mice.

Allergen sensitization and high rates of concomitant allergic diseases are characteristic of severe pediatric asthma. The ovalbumin (OVA)-induced allergic asthma model has been used to investigate the mechanism of allergic asthma. In this study, bioinformatics analysis found that the upregulation of absent in melanoma 2 (AIM2) gene expression in white blood cells from severe pediatric asthma patients compared with normal control subjects. AIM2 might be correlated with cellular immunologic response and the Nucleotide-binding oligomerization domain (NOD) pathway (inflammasome). In an infant mouse model of OVA-induced allergic asthma model, AIM2 knockdown with intranasal administration of a lentivirus ameliorated OVA treatment caused elevation in airway hyper-responsiveness (AHR), elevation in cell quantities (eosinophils, neutrophils, lymphocytes), and increases in the levels of cytokines (IL-4, IL-13, TNF-α, and OVA-specific IgE) in bronchoalveolar lavage fluid (BALF). Moreover, AIM2 knockdown relieved OVA-caused histopathological alterations in mouse lungs, OVA-induced up-regulation of AIM2 levels, and OVA-induced increases in NOD1 and receptor-interacting protein 2 (RIP2) protein levels, as well as p65 phosphorylation. In house dust mite (HDM)-stimulated human bronchial epithelial cell line 16HBE14o, AIM2 knockdown partially ameliorated HDM-induced epithelial dysfunctions by promoting cell viability, down-regulating the levels of IL-4, IL-13, TNF-α, and OVA-specific IgE, decreasing the protein levels of AIM2, NOD1, and RIP2, and suppressing p65 phosphorylation. In conclusion, AIM2, up-regulated in severe pediatric allergic asthma, participates in HDM-induced epithelial dysfunctions and OVA-induced allergic asthma progression. Therefore, AIM2 could be a promising target for pediatric allergic asthma treatment regimens, which warrants further in vivo investigations.