Lymphocyte-stromal cell interaction induces IL-7 expression by interferon regulatory factors.
Lymphocyte-stromal cell interaction induces IL-7 expression by interferon regulatory factors.
复制标题
淋巴细胞-基质细胞相互作用通过干扰素调节因子诱导 IL-7 表达。
DOI：
10.1016/j.molimm.2013.01.002
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发表时间：
2013
期刊：
影响因子：
3.6
通讯作者：
Ikuta K.
中科院分区：
文献类型：
--
作者：
Sekai M;Tani-ichi S;Yoneyama M;Fujita T;Kina T;Ikuta K.
淋巴细胞与基质细胞之间的相互作用在早期淋巴细胞的协调发育中起着重要作用。IL-7是由胸腺和骨髓中的基质细胞产生的早期淋巴细胞发育的必需细胞因子。虽然IL-7是由早期淋巴细胞和基质细胞相互作用诱导的，但其分子基础仍不清楚。为了解决这个问题，我们采用了与IL-7依赖性前B细胞系DW 34和胸腺基质细胞系TSt-4的共培养系统。与DW 34细胞共培养提高了TSt-4细胞中IL-7转录物的水平。有趣的是，共培养物也诱导IFN-α和IFN-β的转录，但不诱导IFN-γ的转录。此外，外源性IFN-β刺激增加了TSt-4细胞中IL-7转录物的水平。接下来，为了阐明IL-7诱导的分子机制，我们通过报告基因测定分析了IL-7启动子活性。IL-7启动子在TSt-4细胞中表现出特异的转录活性。IL-7启动子中的干扰素刺激反应元件（ISRE）对于通过共培养和IFN-β刺激诱导IL-7转录是必不可少的。最后，野生型和显性阴性形式的干扰素调节因子（IRFs）的过表达分别激活和抑制TSt-4细胞中的IL-7启动子。总的来说，这些结果表明，IRFs激活淋巴细胞粘附诱导IL-7转录通过ISRE在基质细胞和I型干扰素可能参与IRFs的激活。因此，这项研究暗示了IFN/IRF信号在淋巴细胞发育过程中的生理功能。
The interaction between lymphocytes and stromal cells plays important roles in coordinated development of early lymphocytes. IL-7 is an essential cytokine for early lymphocyte development produced by stromal cells in the thymus and bone marrow. Although IL-7 is induced by interaction of early lymphocytes and stromal cells, its molecular basis is still unknown. To address this question, we employed co-culture system with an IL-7-dependent pre-B cell line, DW34, and a thymic stromal cell line, TSt-4. Co-culture with DW34 cells enhanced the levels of IL-7 transcripts in TSt-4 cells. Interestingly, the co-culture also induced transcripts of IFN-α and IFN-β but not of IFN-γ. In addition, exogenous IFN-β stimulation increased the levels of IL-7 transcripts in TSt-4 cells. Next, to elucidate the molecular mechanism of IL-7 induction, we analyzed the IL-7 promoter activity by reporter assay. The IL-7 promoter showed specific transcriptional activity in TSt-4 cells. An interferon-stimulated response element (ISRE) in the IL-7 promoter was essential for the induction of IL-7 transcription by both co-culture and IFN-β stimulation. Finally, overexpression of wild-type and dominant-negative forms of interferon regulatory factors (IRFs) activated and repressed, respectively, the IL-7 promoter in TSt-4 cells. Collectively, these results suggested that IRFs activated by lymphocyte adhesion induce IL-7 transcription through ISRE in stromal cells and that type I IFNs may be involved in the activation of IRFs. Thus, this study implied a physiological function of the IFN/IRF signal during lymphocyte development.