Tumor necrosis factor-α promotes granulocyte-macrophage colony-stimulating factor-stimulated microglia to differentiate into competent dendritic cell-like antigen-presenting cells

Abstract

Objective: To examine whether microglia differentiate to dendritic cells (DC) and those DCs can acquire the full characteristic phenotype of mature stimulatory DCs to participate in functional responses. Methods: Isolated microglia were stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and further with lipopolysaccharide (LPS) and/or tumor necrosis factor-α (TNF-α), then phenotypical changes were analysed by their surface antigen expression, cytokine profile and ability to present antigens. Results: Microglia acquire DC markers in the presence of GM-CSF. These GM-CSF-stimulated microglia still do not fully differentiate into mature DCs because of the low expression of mature DC marker CD83 and the high expression of immature DC marker CD209. However, TNF-α further induces their differentiation into DC-like cells by up-regulating the expression of DC-associated antigens. These cells differentiate into CD11c+, CD83high and CD209low mature DCs upon LPS stimulation, effectively present antigen to CD4+ T cells in an antigen-specific manner, and produce DC-like cytokines such as interleukin (IL)-23 and IL-12 as well as pro-inflammatory cytokines such as IL-6 and TNF-α. Conclusions: The resident microglia may become mature DCs and function as stimulatory DCs to induce inflammatory autoimmune responses in the CNS. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759-1961.2010.00016.x, January 2011)