Interleukin-27 directly induces differentiation in hematopoietic stem cells
Interleukin-27 directly induces differentiation in hematopoietic stem cells
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DOI：
10.1182/blood-2007-06-093328
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发表时间：
2008-02-15
期刊：
影响因子：
20.3
通讯作者：
Yoshimoto, Takayuki
中科院分区：
文献类型：
--
作者：
Seita, Jun;Asakawa, Masayuki;Yoshimoto, Takayuki
白细胞介素 (IL)-27 是最近发现的 IL-6 家族细胞因子之一，可激活信号转导子和转录激活子 (STAT)1 和 STAT3，并在促炎和抗炎免疫反应中发挥多种作用。 IL-27通过常见的信号转导受体gp130及其特异性受体WSX-1作用于包括T、B和巨噬细胞在内的多种类型细胞，但IL-27对造血干细胞（HSC）的作用仍不清楚。在这里，我们证明 IL-27 与干细胞因子 (SCF) 一起直接作用于 HSC，并支持其在体外和体内的早期分化。 CD34(-/low)c-Kit(+)Sca(-1) (+)谱系标记(-) (CD34(-)KSL)细胞是小鼠HSC中高度富集的细胞群，被发现表达两种IL-27受体亚基。 CD34-KSL细胞与IL-27和SCF的体外培养导致祖细胞的扩增，包括短期再增殖细胞，同时它们的一些长期再增殖活性也得以维持。为了检查其体内效果，产生了表达 IL-27 的转基因小鼠。这些小鼠表现出骨髓生成增强、骨髓中 B 淋巴细胞生成受损，而脾脏中出现髓外造血。此外，IL-27对人CD34(+)细胞也有类似的作用。这些结果表明 IL-27 是在 HSC 调节中发挥作用的有限细胞因子之一。
Interleukin (IL)-27, one of the most recently discovered IL-6 family cytokines, activates both the signal transducer and activator of transcription (STAT)1 and STAT3, and plays multiple roles in proand anti-inflammatory immune responses. IL-27 acts on various types of cells including T, B, and macrophage through the common signal-transducing receptor gp130 and its specific receptor WSX-1, but the effect of IL-27 on hematopoietic stem cells (HSCs) remains unknown. Here, we show that IL-27 together with stem cell factor (SCF) directly acts on HSCs and supports their early differentiation in vitro and in vivo. CD34(-/low)c-Kit(+)Sca(-1) (+) lineage marker(-) (CD34(-)KSL) cells, a population highly enriched in mouse HSCs, were found to express both IL-27 receptor subunits. In vitro cultures of CD34-KSL cells with IL-27 and SCF resulted in an expansion of progenitors including short-term repopulating cells, while some of their long-term repopulating activity also was maintained. To examine its in vivo effect, transgenic mice expressing IL-27 were generated. These mice exhibited enhanced myelopoiesis and impaired B lymphopoiesis in the bone marrow with extramedullary hematopoiesis in the spleen. Moreover, IL-27 similarly acted on human CD34(+) cells. These results suggest that IL-27 is one of the limited cytokines that play a role in HSC regulation.