In regulon analysis, EPAS1, SMAD3, and SMAD4 regulons were highly upregulated in alveolar macrophages in AATD (Fig 2H), whereas the RELA, NFkB1, ATF6, and ATF4 regulons were upregulated in AT2s in AATD (Fig 2D). This evidence concerns the gene SMAD3 and alpha 1-antitrypsin deficiency.