Department of Hematology, Qilu Hospital, and.
Blood. 2013 Sep 19;122(12):2074-82. doi: 10.1182/blood-2013-03-491555. Epub 2013 Aug 7.
Thalidomide (THD) is an immunomodulatory agent used to treat immune-mediated diseases. Immune thrombocytopenia (ITP) is an autoimmune disorder in which impaired mesenchymal stem cells (MSCs) are potentially involved. We demonstrated that MSCs in ITP patients had reduced proliferative capacity and lost their immunosuppressive function, which could be corrected with THD treatment. According to the gene profile, the downregulation of caspase-8 and caspase-10, and upregulation of oct3/4 and tgf-β1, may be associated with THD modulation. Dendritic cells (DCs) played an important role in mediating the inhibitory activity of MSCs. To study the functional alteration of DCs elicited by MSCs, we sorted DCs after incubation with MSCs and performed T-lymphocyte reaction assays. The THD-modulated MSCs from ITP patients induced mature DCs to become tolerogenic DCs, whereas unmodulated MSCs had no effect. The induction of tolerogenicity in DCs by MSCs was dependent on the expression of TIEG1 in DCs. The study reveals the inability of MSCs from ITP patients to induce tolerogenic ability in DCs. THD could restore the regulatory effect of MSCs on DCs. These findings will help us understand the pathogenesis of ITP, and with appropriate safeguards, THD may benefit patients with ITP.
沙利度胺（THD）是一种免疫调节剂，用于治疗免疫介导的疾病。免疫性血小板减少症（ITP）是一种自身免疫性疾病，其中受损的间充质干细胞（MSCs）可能涉及其中。我们证明，ITP 患者的 MSCs 增殖能力降低，丧失了免疫抑制功能，而 THD 治疗可以纠正这种功能障碍。根据基因谱，caspase-8 和 caspase-10 的下调，以及 oct3/4 和 tgf-β1 的上调，可能与 THD 的调节有关。树突状细胞（DCs）在介导 MSCs 的抑制活性方面发挥着重要作用。为了研究 MSC 引起的 DC 功能改变，我们在与 MSC 孵育后对 DC 进行分选，并进行 T 淋巴细胞反应试验。来自 ITP 患者的 THD 调节的 MSC 诱导成熟 DC 成为耐受原性 DC，而未调节的 MSC 则没有这种作用。MSC 诱导 DC 产生耐受性依赖于 DC 中 TIEG1 的表达。该研究揭示了 ITP 患者的 MSC 无法诱导 DC 产生耐受原性能力。THD 可以恢复 MSC 对 DC 的调节作用。这些发现将帮助我们了解 ITP 的发病机制，并且在适当的保护措施下，THD 可能有益于 ITP 患者。
