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

Abstract

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.