IL4 and chronic obstructive pulmonary disease: An animal study reported that PM2.5-induced M2 AM polarization upregulated the level of MMP12 via the IL-4/STAT6 pathway in mice (42), while another research indicated that IL-4-induced M2 interstitial macrophages (IMs), rather than AMs, appeared to be the major producer of MMP-12 in lungs of COPD mice (43) However, similarly, both of these studies found that M2 macrophages caused the dysfunction of the alveolar epithelial barrier and ultimately led to COPD progression, suggesting that MMP-12 secreted by M2 phenotype may play an important role in the formation of emphysema signs in COPD.