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.
Shibasaki
Tetsunori
T
Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Katayama
Naoyuki
N
Ohishi
Kohshi
K
Fujieda
Atsushi
A
Monma
Fumihiko
F
Nishi
Kazuhiro
K
Masuya
Masahiro
M
Shiku
Hiroshi
H
D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism / Q000502:physiology*; D007801:Langerhans Cells / Q000166:cytology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D015820:Cadherins; D007377:Interleukin-3; D018950:Lipopolysaccharide Receptors; D053773:Transforming Growth Factor beta1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor