Mitchell Peter, Afzali Behdad, Lombardi Giovanna, Lechler Robert I
Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London, UK.
Curr Opin Organ Transplant. 2009 Aug;14(4):326-31. doi: 10.1097/MOT.0b013e32832ce88e.
Regulatory T cells (Tregs) are potential therapeutic tools in averting transplant rejection and promoting lifelong tolerance. However, Tregs can be subverted by inflammatory conditions, resulting in a T helper 17 (Th17) cell response. This review looks at the relationship between Tregs and Th17 cells.
Both naturally occurring and transforming growth factor-beta-induced Tregs can be converted into Th17 cells in the presence of inflammatory cytokines. Transforming growth factor-beta upregulates the Treg transcription factor, forkhead box P3, as well as the Th17 transcription factor, retinoic acid receptor-related orphan receptor gamma. However, forkhead box P3 binds to retinoic acid receptor-related orphan receptor gamma, inhibiting its promotion of IL-17 gene transcription. Inflammatory cytokines can disrupt this interaction through the inhibition of forkhead box P3 expression by signal transducer and activator of transcription 3.
The plasticity of the Treg population during inflammation presents a challenge to the use of Tregs as a therapeutic tool in solid organ transplantation. Investigations into the Th17-Treg axis have identified a number of potential pharmacological targets to avoid the risk of conversion to Th17 cells, but further work must be done before we can separate the benefits of Treg therapy from the hazards of the Th17 response.
调节性T细胞（Tregs）是预防移植排斥和促进终身耐受的潜在治疗工具。然而，Tregs可能会被炎症状态颠覆，从而引发辅助性T细胞17（Th17）细胞反应。本综述探讨Tregs与Th17细胞之间的关系。
在炎性细胞因子存在的情况下，天然存在的和转化生长因子-β诱导的Tregs都可转化为Th17细胞。转化生长因子-β上调Treg转录因子叉头框P3以及Th17转录因子视黄酸受体相关孤儿受体γ。然而，叉头框P3与视黄酸受体相关孤儿受体γ结合，抑制其对IL-17基因转录的促进作用。炎性细胞因子可通过转录信号转导子和激活子3抑制叉头框P3表达来破坏这种相互作用。
炎症期间Treg群体的可塑性对将Tregs用作实体器官移植治疗工具构成了挑战。对Th17-Treg轴的研究已确定了一些潜在的药理学靶点，以避免转化为Th17细胞的风险，但在我们能够将Treg治疗的益处与Th17反应的危害区分开来之前，还必须开展进一步的工作。
