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). The gene discussed is SMAD4; the disease is alpha 1-antitrypsin deficiency.