Human mesenchymal stromal cells modulate T-cell responses through TNF-α-mediated activation of NF-κψB
Human mesenchymal stromal cells modulate T-cell responses through TNF-α-mediated activation of NF-κψB
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DOI：
10.1002/eji.201343668
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发表时间：
2014-02-01
影响因子：
5.4
通讯作者：
Trigueros, Cesar
中科院分区：
文献类型：
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作者：
Dorronsoro, Akaitz;Ferrin, Izaskun;Trigueros, Cesar
虽然间充质基质细胞（MSC）具有调节免疫反应的能力，但对这些过程的机制知之甚少。在这项研究中，我们表明，免疫抑制是由核因子κ B（NF-B）在人骨髓间充质干细胞的激活介导的。该途径由TCR刺激T细胞后产生的TNF-α激活。通过沉默IB激酶或TNF-受体抑制NF-B消除了MSC的免疫抑制能力。我们的数据还表明，MSC相关的NF-B活化主要导致T细胞增殖的抑制，而对活化标志物CD 69和CD 25的表达几乎没有影响。因此，我们的数据支持的假设，TNF-/NF-B信号通路所需的免疫抑制功能在人MSC的初始启动。有趣的是，干扰NF-B活化的药物显著拮抗MSC的免疫调节作用，这可能对临床免疫抑制方案具有重要意义。
Although mesenchymal stromal cells (MSCs) possess the capacity to modulate immune responses, little is known about the mechanisms that underpin these processes. In this study, we show that immunosupression is mediated by activation of nuclear factor kappa B (NF-B) in human MSCs. This pathway is activated by TNF- that is generated following TCR stimulation of T cells. Inhibition of NF-B through silencing of IB kinase or the TNF- receptor abolishes the immunosuppressive capacity of MSCs. Our data also indicate that MSC-associated NF-B activation primarily leads to inhibition of T-cell proliferation with little effect on expression of the activation markers CD69 and CD25. Thus, our data support the hypothesis that the TNF-/NF-B signalling pathway is required for the initial priming of immunosuppressive function in human MSCs. Interestingly, drugs that interfere with NF-B activation significantly antagonise the immunoregulatory effect of MSCs, which could have important implications for immunosuppression regimens in the clinic.