IL-17-producing human peripheral regulatory T cells retain suppressive function
IL-17-producing human peripheral regulatory T cells retain suppressive function
复制标题
DOI：
10.1182/blood-2008-10-183251
复制
发表时间：
2009-04-30
期刊：
影响因子：
20.3
通讯作者：
Hafler, David A.
中科院分区：
文献类型：
--
作者：
Beriou, Gaelle;Costantino, Cristina M.;Hafler, David A.
尽管调节性T细胞(Tregs)和Th17效应细胞都具有拮抗功能，但它们在控制自身免疫发病机制中发挥着重要作用。矛盾的是，最近的研究表明Treg细胞具有产生白细胞介素17(IL-17)的能力，尽管这些细胞保持其抑制功能的能力尚不清楚。在此，我们报道了在致炎细胞因子IL-1β和IL-6存在的情况下，CD4(+)CD45RA(-)CD25(High)CCR6(+)HLA-DR(-)FoxP3(+)群体中的人Tregs产生IL-17，而IL-17的分泌被转化生长因子β抑制。为了评估单个Treg分泌IL-17和抑制体外免疫功能的能力，我们从这个群体中分离出克隆。我们发现IL-17(+)/FoxP3(+)Treg克隆保留了抑制功能，并根据刺激的性质表现出分泌IL-17或抑制的可塑性。这些Treg克隆产生IL-17的同时伴随着FoxP3的持续表达和可逆的抑制活性的丧失。我们的数据表明，在单细胞水平上，在炎症条件下，体外抑制FoxP3(+)细胞的亚群可以被驱动分泌IL-17。这些发现表明了一种新的机制，通过这种机制，炎症可以驱动Treg分泌IL-17，从而抑制抑制并促进炎症环境。(血。2009；113：4240-4249)
Although implicated in antagonistic functions, both regulatory T cells (Tregs) and Th17 effector cells play an important role in controlling autoimmune pathogenesis. Paradoxically, recent studies indicate that Tregs have the capacity to produce interleukin-17 (IL-17), although the ability of these cells to retain their suppressive function remains unknown. Here we report that human Tregs within the CD4(+) CD45RA(-) CD25(high)CCR6(+) HLA-DR(-)FoxP3(+) population produce IL-17 when activated in the presence of the proinflammatory cytokines IL-1 beta and IL-6, whereas IL-17 secretion was inhibited by TGF beta. To assess the ability of a single Treg to secrete IL-17 and to suppress in vitro immune function, we isolated clones from this population. We found that IL-17(+)/FoxP3(+) Treg clones retain suppressive function and exhibit the plasticity to secrete IL-17 or suppress depending on the nature of the stimulus provided. IL-17 production by these Treg clones was accompanied by sustained FoxP3 expression and concomitant, but reversible, loss of suppressive activity. Our data demonstrate that at the single cell level a subset of in vitro suppressive FoxP3(+) cells can be driven to secrete IL-17 under inflammatory conditions. These findings suggest a new mechanism by which inflammation can drive Tregs to secrete IL-17, thereby dampening suppression and promoting an inflammatory milieu. ( Blood. 2009;113:4240-4249)