Human thymic stromal lymphopoietin preferentially stimulates myeloid cells

Human thymic stromal lymphopoietin preferentially stimulates myeloid cells
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DOI:
10.4049/jimmunol.167.1.336
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发表时间:
2001-07-01
影响因子:
4.4
通讯作者:
Bazan, JF
Bazan, JF
中科院分区:
医学2区
文献类型:
--
作者:
Reche, PA;Soumelis, V;Bazan, JF

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在基因组数据库的计算筛选中发现了一种新的造血细胞因子的序列,其与小鼠胸腺基质淋巴细胞生成素(TSLP)的同源性表明它是人类的直系同源物。提出人TSLP通过异源二聚体受体复合物发出信号,所述异源二聚体受体复合物由称为人TSLP受体的促红细胞生成素家族的新成员和IL-7 R α链组成。两种受体亚基转染的细胞增殖响应纯化的重组人TSLP,诱导磷酸化的Stat 3和Stat 5。人TSLPR和IL-7 Ra主要在单核细胞和树突细胞群上共表达,在各种淋巴样细胞上共表达的程度要小得多。与此雅阁,我们发现人TSLP主要作用于髓系细胞;它诱导单核细胞释放T细胞吸引趋化因子,特别是增强CD 11 c(+)树突状细胞的成熟,如通过强烈诱导共刺激分子CD 40和CD 80以及增强诱导幼稚T细胞增殖的能力所证明的。
The sequence of a novel hemopoietic cytokine was discovered in a computational screen of genomic databases, and its homology to mouse thymic stromal lymphopoietin (TSLP) suggests that it is the human orthologue. Human TSLP is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human TSLP receptor and the IL-7R a-chain. Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. Human TSLPR and IL-7R alpha are principally coexpressed on monocytes and dendritic cell populations and to a much lesser extent on various lymphoid cells. In accord, we find that human TSLP functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells, as evidenced by the strong induction of the costimulatory molecules CD40 and CD80 and the enhanced capacity to elicit proliferation of naive T cells.