The role of autophagy in allergic inflammation: a new target for severe asthma

Autophagy has been investigated for its involvement in inflammatory diseases, but its role in asthma has been little studied. This study aimed to explore the possible role of autophagy and its therapeutic potential in severe allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) on days 0 and 14, followed by primary OVA challenge on days 28–30. The mice received a secondary 1 or 2% OVA challenge on days 44–46. After the final OVA challenge, the mice were assessed for airway responsiveness (AHR), cell composition and cytokine levels in bronchoalveolar lavage fluid (BALF). LC3 expression in lung tissue was measured by western blot and immunofluorescence staining. Autophagosomes were detected by electron microscopy. 3-Methyladenine (3-MA) treatment and Atg5 knockdown were applied to investigate the potential role of autophagy in allergic asthma mice. AHR, inflammation in BALF and LC3 expression in lung tissue were significantly increased in the 2% OVA-challenged mice compared with the 1% OVA-challenged mice (P<0.05). In addition, eosinophils showed prominent formation of autophagosomes and increased LC3 expression compared with other inflammatory cells in BALF and lung tissue. After autophagy was inhibited by 3-MA and Atg5 shRNA treatment, AHR, eosinophilia, interleukin (IL)-5 levels in BALF and histological inflammatory findings were much improved. Finally, treatment with an anti-IL-5 antibody considerably reduced LC3 II expression in lung homogenates. Our findings suggest that autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. The extent of cellular cleanup in inflammatory immune cells is tightly linked to the severity of allergic asthma, a study in mice finds. Yoo Seob Shin from Ajou University School of Medicine, South Korea, and colleagues looked at how immune cells called eosinophils package and destroy cellular debris, a process known as autophagy, in a mouse model of severe allergic asthma. They found a correlation between markers of disease severity in the lung tissue of the mice and the formation of autophagosomes, specialized structures that contain the cellular material destined for degradation by autophagy. Experimentally blocking autophagy in various ways reduced the number of eosinophils and the degree of inflammatory damage in the mouse lungs. The findings suggest that drugs targeting autophagy may provide a new way of treating severe allergic asthma.