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.
Xiao
Bao-Guo
BG
Experimental Neurology Unit, Division of Neurology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden. bao-guo.xiao@neurotec.ki.se
Xu
Ling-Yun
LY
Yang
Jian-She
JS
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D066298:In Vitro Techniques; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor