TLR4 and pulmonary emphysema: The clinical relevance of this study is supported by data from our laboratory and others; (a) TLR4 expression is decreased in human COPD lungs (Lee et al., 2012; Speletas et al., 2009), (b) TLR4 expression decreases in Ec as they age, the most common risk factor for emphysema/COPD, and (c) many of the senescence and epigenetic molecular changes found in TLR4−/− lungs and Ec are also found in human COPD lungs (Ito et al., 2005; Qu et al., 2013; Tsuji et al., 2006).