Institute of Hematology, Department of Hematology and Oncological Sciences L. e A. Seràgnoli, University of Bologna, Bologna, Italy.
Ann Hematol. 2013 Jan;92(1):67-78. doi: 10.1007/s00277-012-1556-5. Epub 2012 Aug 31.
Along with their immunogenic role, dendritic cells (DCs) are also critical in maintaining tolerance to self-antigens by inducing regulatory T cells (Tregs) via the expression of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1). In turn, Tregs modulate the maturation and/or function of DCs. In immune thrombocytopenia (ITP), the interaction between DCs and Tregs has never been investigated although decreased number/function of Tregs as well as altered DCs have been described. Here, we ask whether, in ITP: (1) IDO1 expression/activity is decreased in mature DCs; (2) IDO1-mediated Treg generation is impaired; and (3) DC maturation is abnormally modulated by Tregs. We found that in ITP, DCs show reduced capability of upregulating the expression/activity of IDO1. This finding results in the reduced ability of mature DCs of converting T cells into Tregs. In turn, Tregs are characterized by decreased interleukin-10 production and show lower ability of inhibiting DC maturation. In conclusion, these data point out the role of IDO1 in the impaired regulatory T cell development of ITP patients and suggest that the cross-talk between Tregs and DCs is hampered and plays a pathogenetic role.
树突状细胞（DCs）除了具有免疫原性作用外，还通过表达免疫调节酶吲哚胺 2,3-双加氧酶 1（IDO1）诱导调节性 T 细胞（Tregs），从而在维持对自身抗原的耐受方面也起着至关重要的作用。反过来，Tregs 调节 DCs 的成熟和/或功能。在免疫性血小板减少症（ITP）中，尽管已经描述了 Tregs 的数量/功能减少以及 DCs 的改变，但 DCs 和 Tregs 之间的相互作用从未被研究过。在这里，我们询问在 ITP 中：（1）成熟 DCs 中 IDO1 的表达/活性是否降低；（2）IDO1 介导的 Treg 生成是否受损；以及（3）Tregs 是否异常调节 DC 成熟。我们发现，在 ITP 中，DCs 上调 IDO1 的表达/活性的能力降低。这一发现导致成熟 DC 转化 T 细胞为 Treg 的能力降低。反过来，Tregs 的白细胞介素-10 产生减少，并且抑制 DC 成熟的能力降低。总之，这些数据指出了 IDO1 在 ITP 患者调节性 T 细胞发育受损中的作用，并表明 Tregs 和 DCs 之间的相互作用受阻，并发挥了致病作用。
