Autophagy and inflammation in chronic respiratory disease

Abstract

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. AbbreviationsAR allergic rhinitisAM alveolar macrophageATG autophagy-relatedCF cystic fibrosisCFTR cystic fibrosis transmembrane conductance regulatorCOPD chronic obstructive pulmonary diseaseCS cigarette smokeCSE cigarette smoke extractDC dendritic cellIH intermittent hypoxiaIPF idiopathic pulmonary fibrosisILD interstitial lung diseaseMAP1LC3B microtubule associated protein 1 light chain 3 betaMTBMycobacterium tuberculosisMTOR mechanistic target of rapamycin kinaseNET neutrophil extracellular trapsOSA obstructive sleep apneaPAH pulmonary arterial hypertensionPH pulmonary hypertensionROS reactive oxygen speciesTGFB1 transforming growth factor beta 1TNF tumor necrosis factor.