TGF-beta 1 synergizes with GM-CSF to promote the generation of glial cell-derived dendriform cells in vitro.

Microglia are often considered a type of tissue macrophages analogous Langerhans' cells, while dendritic cells (DC) can be generated in vitro from cultured microglia in the presence of GM-CSF. In this study, we show that TGF-beta 1, in the presence of GM-CSF, promoted the growth and differentiation of glial cell-derived dendritic cells (GC-DC). TGF-beta 1-driven GC-DC exhibited an immature state reflected by low CD11c expression, augmented endocytosis, and reduced antigen presentation. Expression of Fas was inhibited in GM-CSF+TGF-beta 1-supplemented cell cultures and may relate to a long life span of GC-DC treated with GM-CSF+TGF-beta 1. IL-10 and IL-12 mRNA on GC-DC was not affected upon exposure to GM-CSF alone or to GM-CSF+IFN-gamma, GM-CSF+IL-10 or GM-CSF+TGF-beta 1. In sharp contrast, TGF-beta 1, in the presence of GM-CSF, dramatically up-regulated the expression of TNF-alpha and TGF-beta 1 mRNA. These results demonstrate that TGF-beta 1 seems to play a crucial role in the differentiation, functional skewing, and cytokine profile of GC-DC. TGF-beta 1-driven GC-DC awaits further investigation to facilitate a better understanding of the glia-T cell dialog as well as the pathogenesis and immunotherapy of central nervous system inflammatory and degenerative diseases.