Autophagy functions in lung macrophages and dendritic cells to suppress TH17 responses and neutrophil accumulation during allergic airway inflammation

Asthma affects nearly 260 million people worldwide, where severe asthma cases represent the most difficult to treat due to corticosteroid insensitivity. Severe asthma is associated with higher levels of TH17 and TH1 responses, accompanied by neutrophil dominated inflammation. Better understanding of the immune responses to airway allergens that promote or protect against severe asthma is critical for identifying ways to treat these patients. Single nucleotide polymorphisms in the ATG5 gene, which encodes for a protein required for the cellular recycling process of autophagy, has been associated with higher risk for developing severe asthma. However, the exact role for ATG5 during allergic inflammation and whether other autophagy proteins are involved remains elusive. Using genetic tools to dissect the roles for ATG5 in innate immune cells in house dust mite (HDM)-challenged mice, we have identified a specific role for ATG5 in CD11c+ lung macrophages and dendritic cells for suppressing TH17 responses and neutrophil accumulation. We found that this role for ATG5 in CD11c+ cells to regulate neutrophil accumulation during allergic airway inflammation also required other autophagy proteins but did not involve regulation of inflammasome, despite higher levels of IL-1β and Caspase 1 in the lungs of mice lacking autophagy in innate immune cells. Our data support a role for autophagy in CD11c+ lung macrophages and dendritic cells to promote an immune response to airway allergens that is associated with less severe asthma by suppressing TH17 responses and neutrophil accumulation in the lung.