Autophagy and inflammation in chronic respiratory disease

Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases including chronic obstructive pulmonary disease, asthma and pulmonary fibrosis. Chronic inflammation in the lung may arise from a combination of genetic susceptibility and environmental influences, including exposure to microbes, particles from the atmosphere, irritants, pollutants, allergens, and toxic molecules. To this end, an immediate, strong, and highly regulated inflammatory defense mechanism is needed for the successful maintenance of homeostasis within the respiratory system. Macroautophagy/autophagy plays an essential role in the inflammatory response of the lung to infection and stress. At baseline, autophagy may be critical for inhibiting spontaneous pulmonary inflammation and fundamental for the response of pulmonary leukocytes to infection; however, when not regulated, persistent or inefficient autophagy may be detrimental to lung epithelial cells, promoting lung injury. This perspective will discuss the role of autophagy in driving and regulating inflammatory responses of the lung in chronic lung diseases with a focus on potential avenues for therapeutic targeting. AbbreviationsARallergic rhinitisAMalveolar macrophageATGautophagy-relatedCFcystic fibrosisCFTRcystic fibrosis transmembrane conductance regulatorCOPDchronic obstructive pulmonary diseaseCScigarette smokeCSEcigarette smoke extractDCdendritic cellIHintermittent hypoxiaIPFidiopathic pulmonary fibrosisILDinterstitial lung diseaseMAP1LC3Bmicrotubule associated protein 1 light chain 3 betaMTBMycobacterium tuberculosisMTORmechanistic target of rapamycin kinaseNETneutrophil extracellular trapsOSAobstructive sleep apneaPAHpulmonary arterial hypertensionPHpulmonary hypertensionROSreactive oxygen speciesTGFB1transforming growth factor beta 1TNFtumor necrosis factor