The Role of Autophagy in Allergic Inflammation: A New Target for Severe Asthma

Rationale: Autophagy has been investigated to be involved in inflammatory diseases, but its implications in asthma have rarely been studied. This study aimed to explore the possible role of autophagy and its therapeutic potentials in severe allergic asthma.

Methods: BALB/c mice were sensitized by ovalbumin (OVA) on days 0 and 14, followed by primary OVA challenges on day 28-30. Mice received a secondary 1% or 2% OVA challenges on days 44-46. After the final OVA challenge, 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), Atg5 knockdown and anti-IL5 antibody were applied to investigate the potential role of autophagy in allergic asthma mice.

Results: The AHR, inflammation in BALF and LC3 expression in lung tissue were significantly increased in 2% OVA challenged mice compared to those of 1% OVA challenged mice (P < 0.05). Additionally, eosinophils showed prominently formation of autophagosomes and increase LC3 expression compared with other inflammatory cells in BALF and lung tissue. After inhibiting autophagy by 3-MA and Atg5 shRNA, the AHR, eosinophilia, IL-5 level in BALF, and inflammatory findings in histology were significantly improved. Finally, treatment of anti-IL-5 antibody considerably reduced LC3 II expression in lung homogenate.

Conclusions: 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.