Colony-stimulating factor-1 secreted by fibroblasts promotes the growth of dendritic cell lines (XS series) derived from murine epidermis

We have established recently from mouse epidermis long-term dendritic cell lines (XS series) that resemble epidermal Langerhans cells (LC) by their surface phenotype, Ag presenting profile and cytokine mRNA profile. The growth of XS lines was promoted maximally by granulocyte-macrophage-CSF or by a factor secreted by NS lines, which are fibroblastic cell lines established from dispase-separated specimens of mouse epidermis. The purpose of this study was to determine the identity of XS cell-growth factor secreted by NS cells. We report the following: 1) NS cells express constitutively mRNA for CSF-1; 2) XS cells express the CSF-1R at mRNA and protein levels; 3) rCSF-1 mimics NS culture supernatant in its ability to promote XS cell growth; 4) NS supernatant-dependent XS cell growth is blocked completely by each of two Abs against the CSF-1R. We conclude that CSF-1 is responsible for the XS growth- promoting activity secreted by NS lines. We also report the following: 5) LC freshly isolated from skin express CSF-1R mRNA; and 6) fibroblasts derived from specimens of dermis also express mRNA and secrete large amounts (50-100 ng/ml) of CSF-1. These observations give rise to a new concept that dermal fibroblasts may support the survival and growth of LC (and their precursors) through the paracrine effect of elaborated CSF-1.