IL-3 Can Not Replace GM-CSF in Inducing Human Monocytes to Differentiate into Langerhans Cells

Receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) share a common beta subunit. We recently reported that GM-CSF acts in concert with transforming growth factor-beta1 (TGF-beta1) and Notch ligand Delta-1 (Delta-1) to promote the differentiation of human blood monocytes into Langerhans cells. In the present study, we examined whether IL-3, in place of GM-CSF, can induce the development of Langerhans cells from blood monocytes in the presence of TGF-beta1 and Delta-1, because the IL-3 receptor alpha chain was substantially expressed on monocytes. However, the generation of Langerhans cells was not obtained by the combination of IL-3, TGF-beta1 and Delta-1, even though GM-CSF and IL-3 exhibited a similar effect with respect to the differentiation of monocytes into macrophages and dendritic cells. The addition of GM-CSF to the culture supplemented with IL-3, TGF-beta1 and Delta-1 restored the differentiation of monocytes toward Langerhans cells. A microarray analysis revealed that a number of genes including Langerhans cell markers, E-cadherin and Langerin, were specifically expressed in cells from GM-CSF-containing cultures but not in those from IL-3-containing cultures. These data suggest that IL-3 can not replace GM-CSF to induce the differentiation of human monocytes into Langerhans cells in culture.