To characterize the role of interleukin (IL)-1β and skin microvascular endothelial cells (MECs) in the generation of alternatively-activated macrophages (AAMs) and explore their fibrotic role during systemic sclerosis (SSc).
Conditioned medium from MECs purified from healthy donors (HD) or SSc patient's skin were used to generate monocytes-derived macrophages. Flow cytometry, multiplex protein assessment, RT-qPCR and tissue immunofluorescence were used to characterize MEC-induced AAM polarization. Co-culture experiments were conducted to assess the role of MEC-induced AAM on fibroblast activation. AAMs were characterized in skin of healthy donors and SSc patients using multiparametric immunofluorescence and multiplexed measurements of gene expression. A skin AAM-specific score was developed to perform correlations with clinical features.
IL-1β-activated MECs from SSc patients induced monocytes to differentiate into DC-SIGN
Our work sheds new light on the vicious circle implicating IL-1β unabated secretion, microvascular endothelial cells activation and generation of DC-SIGN