Vogel Christoph F A, Goth Samuel R, Dong Bin, Pessah Isaac N, Matsumura Fumio
Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616, USA.
Biochem Biophys Res Commun. 2008 Oct 24;375(3):331-5. doi: 10.1016/j.bbrc.2008.07.156. Epub 2008 Aug 9.
Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to immune suppression associated with the induction of regulatory T cells (T(reg)) expressing the transcription factor Foxp3. The immunological mechanisms of suppression are not well understood however dendritic cells (DC) are considered a key target for AhR-mediated immune suppression. Here we show that activation of AhR by TCDD induces DC indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase-like protein (IDO2). Induction of IDO1 and IDO2 was also found in lung and spleen associated with an increase of the T(reg) marker Foxp3 in spleen of TCDD-treated C57BL/6 mice, which is suppressed by inhibition of IDO. These data indicate that AhR-activation is an important signaling pathway for IDO expression and suggest a critical role of IDO in the mechanism leading to the generation of T(reg) that mediates the immune suppression through activation of AhR.
2,3,7,8-四氯二苯并对二恶英（TCDD）激活芳烃受体（AhR）会导致免疫抑制，这与诱导表达转录因子Foxp3的调节性T细胞（Treg）有关。然而，抑制的免疫机制尚未完全了解，不过树突状细胞（DC）被认为是AhR介导的免疫抑制的关键靶点。在此我们表明，TCDD激活AhR会诱导DC中的吲哚胺2,3-双加氧酶1（IDO1）和吲哚胺2,3-双加氧酶样蛋白（IDO2）。在TCDD处理的C57BL/6小鼠的肺和脾脏中也发现了IDO1和IDO2的诱导，这与脾脏中Treg标志物Foxp3的增加有关，而IDO的抑制可抑制这种增加。这些数据表明，AhR激活是IDO表达的重要信号通路，并提示IDO在导致Treg产生的机制中起关键作用，Treg通过激活AhR介导免疫抑制。
