Medical University of Graz

Using a myeloid-specific Tsc2 deletion mouse model that recapitulates key features of human cardiac sarcoidosis, and integrating single-cell RNA sequencing, bioinformatic analyses, histopathology, in vitro functional studies in murine and human macrophages, and in vivo pharmacologic inhibition, the study found that constitutive mTORC1 activation induces a fibrogenic macrophage (FibMac) population in the heart characterized by Cd63, Spp1, Gpnmb, and Fabp5 expression and arising through a TGF-β-dependent monocyte-to-FibMac differentiation process, and identified MMP12 as a macrophage-intrinsic inducer and dominant effector of this program: recombinant MMP12 was sufficient to enforce fibrogenic differentiation, clustering, and epithelioid features in mouse and human macrophages, whereas selec

Using a myeloid-specific Tsc2 deletion mouse model that recapitulates key features of human cardiac sarcoidosis, and integrating single-cell RNA sequencing, bioinformatic analyses, histopathology, in vitro functional studies in murine and human macrophages, and in vivo pharmacologic inhibition, the study found that constitutive mTORC1 activation induces a fibrogenic macrophage (FibMac) population in the heart characterized by Cd63, Spp1, Gpnmb, and Fabp5 expression and arising through a TGF-β-dependent monocyte-to-FibMac differentiation process, and identified MMP12 as a macrophage-intrinsic inducer and dominant effector of this program: recombinant MMP12 was sufficient to enforce fibrogenic differentiation, clustering, and epithelioid features in mouse and human macrophages, whereas selec