TY - JOUR T1 - The integrated stress response in pulmonary disease JF - European Respiratory Review JO - EUROPEAN RESPIRATORY REVIEW DO - 10.1183/16000617.0184-2020 VL - 29 IS - 157 SP - 200184 AU - Giulia Emanuelli AU - Nikou Nassehzadeh-Tabriz AU - Nick W. Morrell AU - Stefan J. Marciniak Y1 - 2020/09/30 UR - http://err.ersjournals.com/content/29/157/200184.abstract N2 - The respiratory tract and its resident immune cells face daily exposure to stress, both from without and from within. Inhaled pathogens, including severe acute respiratory syndrome coronavirus 2, and toxins from pollution trigger a cellular defence system that reduces protein synthesis to minimise viral replication or the accumulation of misfolded proteins. Simultaneously, a gene expression programme enhances antioxidant and protein folding machineries in the lung. Four kinases (PERK, PKR, GCN2 and HRI) sense a diverse range of stresses to trigger this “integrated stress response”. Here we review recent advances identifying the integrated stress response as a critical pathway in the pathogenesis of pulmonary diseases, including pneumonias, thoracic malignancy, pulmonary fibrosis and pulmonary hypertension. Understanding the integrated stress response provides novel targets for the development of therapies.By integrating signals from multiple stressors, the integrated stress response plays key roles in the pathophysiology of lung disease. Understanding the mechanisms involved will identify novel means of therapy. https://bit.ly/2Bg2kj4 ER -