Two mouse models for studying smoke‐related interstitial lung diseases

Some subgroups of interstitial lung diseases, namely desquamative interstitial pneumonia (DIP), respiratory bronchiolitis‐associated interstitial pneumonia (RB‐ILD), and pulmonary Langerhans cell histiocytosis, are caused by cigarette smoke (CS) in susceptible individuals. Despite smoke‐related interstitial lung diseases (SRILDs) have been subjected to extensive investigation during the last years, very little is know about the pathogenetic mechanisms of these diseases and why only a susceptible minority of tobacco smokers develop a clinically significant disease. We observed that the combination of chronic cigarette‐smoke exposure with targeted mutation of genes involved in the expression of factors important for adaptive immune responses (namely p56 LcK ), or for the modulation of antioxidant genes (such as p66 Shc ), results in the development of SRILDs. These mice mimic the histopathological traits, which characterise either DIP or RB—ILD in man. Species differences notwithstanding, the data obtained in our mice strongly suggest that DIP cannot be regarded as a late stage of RB—ILD but may represent an earlier (cellular) stage of cryptogenic fibrosing alveolitis. Further studies on these unique animal models may shed light on the pathogenetic mechanisms and the missing links existing among the various SRILDs and can provide valuable information on both the reversibility and the evolution of the histolopathogical changes characterising DIP and/or RB—ILD. This abstract is funded by: MURST, Rome, Italy