间充质的干细胞(MSC ) 为治疗各种各样的疾病有大潜力,特别那些与织物有关损坏包含有免疫力的反应。各种各样的研究证明了 MSC 在 vitro 并且在 vivo 是强烈抑制免疫力的。我们的最近的研究证明了那未刺激的 MSC 确实不能免疫力的抑制;他们与 TNF- 伪, IL-1 伪或 IL-1 尾与激活的淋巴细胞的上层清液,或与 IFN- 纬的联合在刺激之上变得 potently 抑制免疫力。这观察表明在某些情形下面,煽动性的 cytokines 能实际上变得抑制免疫力。我们证明在调停 MSC 的免疫力的抑制的机制有一个种类变化:由告知 cytokine 的老鼠 MSC 的免疫力的抑制被氮的氧化物调停(没有) 而由告知 cytokine 的人的 MSC 的免疫力的抑制通过 indoleamine 被执行 2, 3-dioxygenase (伊多语) 。在有煽动性的 cytokines 的刺激之上,另外,老鼠和人的 MSC 分泌几白血球 chemokines 显然服务与 MSC 吸引有免疫力的房间进最近,在哪儿不或伊多语被预言很活跃。因此,由煽动性的刺激 cytokine 的 MSC 的免疫力的抑制经由 chemokines 的一致行动发生并且免疫者禁止没有或伊多语由 MSC 生产了。因此,我们的结果在对待有免疫力的回答导致的织物损害关于调停 MSC 的免疫力的抑制并且为 MSC 的更好的申请的机制提供新奇信息。
Mesenchymal stem cells (MSCs) have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression: immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide (NO), whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase (IDO). Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.