Pro-fibrotic Activation of Human Macrophages in Systemic Sclerosis

Genome-wide gene expression studies implicate macrophages as mediators of fibrosis in systemic sclerosis (SSc), but little is known about how these cells contribute to fibrotic activation in SSc. Here, we characterized the activation profile of SSc patient monocyte-derived macrophages and assessed their interaction with SSc patient fibroblasts. Plasma and PBMCs were obtained from whole blood of SSc patients (n=24) and healthy age and gender-matched control subjects (n=12). Monocytes were cultured with autologous or allogeneic plasma to differentiate cells into macrophages. For reciprocal activation studies, macrophages were co-cultured with fibroblasts using Transwells. The gene expression signature associated with blood-derived human SSc macrophages was enriched in SSc patient skin from an independent cohort and correlated with skin fibrosis. SSc macrophages expressed surface markers associated with activation and released CCL2, IL-6, and TGF-β under basal conditions (n=8, p