As seen in Fig 10, M1 knockout results in significant reductions of TD and proinflammatory signals to rather low levels despite continuous CS exposure. M1 not only secretes proinflammatory cytokines such as TNF-α, IL-6 and IL-12, but also causes tissue damage as discussed above (Fig 1). Our results are in line with experiments demonstrating that M1 is a determinant for CS-induced COPD .