Transforming growth factor β1 in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells

Transforming growth factor β1 in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells
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DOI:
10.1084/jem.187.6.961
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发表时间:
1998-03-16
影响因子:
15.3
通讯作者:
Hermine, O
Hermine, O
中科院分区:
医学1区
文献类型:
--
作者:
Geissmann, F;Prost, C;Hermine, O

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Langerhans细胞(LCS)是表皮,支气管和粘膜中存在的树突状细胞(DC)。尽管LCS起源于骨髓,但对它们的原始血统知之甚少。在这项研究中,我们证明体外LC可能起源于单核细胞。成年外周血CD14(+)单核细胞分化为LCS(CD1A(+),E-钙粘蛋白(+),皮肤淋巴细胞相关的抗原(+),Birbeck颗粒(+),滞后(+))巨噬细胞刺激因子,白介素4和转化生长因子β1(TGF-β1)。这个过程几乎没有细胞增殖,也不会受到30 Gy辐射的损害。由于单核细胞衍生的DC可以进一步区分LC,因此排除了单核细胞亚群的选择。我们的数据表明,体内LC分化可能是由非增殖的髓样前体(即单核细胞)诱导的,如在皮肤和上皮中所发现的那样。因此,单核细胞可能代表对体内免疫反应至关重要的循环前体。
Langerhans cells (LCs) are dendritic cells (DCs) that are present in the epidermis, bronchi, and mucosae. Although LCs originate in bone marrow, little is known about their lineage of origin. In this study, we demonstrate that in vitro LCs may originate from monocytes. Adult peripheral blood CD14(+) monocytes differentiate into LCs (CD1a(+), E-cadherin(+), cutaneous lymphocyte-associated antigen(+), Birbeck granules(+), Lag(+)) in the presence of granulocyte/macrophage colony-stimulating factor, interleukin 4, and transforming growth factor beta 1 (TGF-beta 1). This process occurs with virtually no cell proliferation and is not impaired by 30 Gy irradiation. Selection of monocyte subpopulations is ruled out since monocyte-derived DCs can further differentiate into LCs. Our data suggest that in vivo LC differentiation may be induced peripherally, from a nonproliferating myeloid precursor, i.e., the monocyte, in response to a TGF-beta 1-rich microenvironment, as found in the skin and epithelia. Therefore, the monocyte may represent a circulating precursor critical to the immune response in vivo.