TGF-β1 synergizes with GM-CSF to promote the generation of glial cell-derived dendriform cells in vitro

• Published in: Brain, behavior, and immunity Vol. 16; no. 6; pp. 685 - 697
• Main Authors: Xiao, Bao-Guo, Xu, Ling-Yun, Yang, Jian-She
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2002
• Subjects: Central nervous system; Glial cell-derived dendritic cells; Glial cells; TGF-β1; TGF-β1; Glial cell-derived dendritic cells; Glial cells; Central nervous system
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/S0889-1591(02)00020-X

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-β1, in the presence of GM-CSF, promoted the growth and differentiation of glial cell-derived dendritic cells (GC–DC). TGF-β1-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-β1-supplemented cell cultures and may relate to a long life span of GC–DC treated with GM-CSF+ TGF-β1. IL-10 and IL-12 mRNA on GC–DC was not affected upon exposure to GM-CSF alone or to GM-CSF+ IFN-γ, GM-CSF + IL-10 or GM-CSF+ TGF-β1. In sharp contrast, TGF-β1, in the presence of GM-CSF, dramatically up-regulated the expression of TNF-α and TGF-β1 mRNA. These results demonstrate that TGF-β1 seems to play a crucial role in the differentiation, functional skewing, and cytokine profile of GC–DC. TGF-β1-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 degener.