AHR-mediated immunomodulation: the role of altered gene transcription.
AHR-mediated immunomodulation: the role of altered gene transcription.
复制标题
DOI：
10.1016/j.bcp.2008.11.021
复制
发表时间：
2009-02-15
影响因子：
5.8
通讯作者：
Kerkvliet, Nancy I.
中科院分区：
文献类型：
--
作者：
Kerkvliet, Nancy I.
免疫系统是芳香烃受体（AHR）介导的转录调节的敏感靶点。大多数参与免疫应答的细胞表达AHR蛋白，并且参与其应答的许多基因在其启动子中含有多个DRE序列。然而，许多这些候选基因在AHR介导的免疫调节中的潜在参与从未被研究过。由于病原体驱动的炎症和适应性免疫反应的复杂性，以及AHR的激活经常影响已经被应答细胞中的其他转录事件调节的基因的表达的事实，存在理解AHR激活的转录效应的许多障碍。TCDD作为最有效的非代谢AHR配体的研究表明，AHR激活改变了许多形成适应性免疫应答的炎症信号，有助于改变抗原特异性CD 4 + T辅助（TH）细胞的分化和改变适应性免疫应答。使用TCDD，大多数适应性免疫应答被高度抑制，这最近与CD 4 + CD 25+调节性T细胞的AHR依赖性诱导有关。然而，某些非TCDD配体激活AHR可能导致其他免疫结果，这是由于配体代谢为活性代谢物或对AHR介导的基因转录的未知配体特异性作用。基于使用AHR−/−小鼠的研究，内源性AHR配体在调节免疫反应中的作用的证据越来越多，胆红素和脂氧素A4代表两个有希望的候选者。
The immune system is a sensitive target for aryl hydrocarbon receptor (AHR)-mediated transcriptional regulation. Most of the cells that participate in immune responses express AHR protein, and many genes involved in their responses contain multiple DRE sequences in their promoters. However, the potential involvement of many of these candidate genes in AHR-mediated immunomodulation has never been investigated. Many obstacles to understanding the transcriptional effects of AHR activation exist, owing to the complexities of pathogen-driven inflammatory and adaptive immune responses, and to the fact that activation of AHR often influences the expression of genes that are already being regulated by other transcriptional events in responding cells. Studies with TCDD as the most potent, non-metabolized AHR ligand indicate that AHR activation alters many inflammatory signals that shape the adaptive immune response, contributing to altered differentiation of antigen specific CD4+ T helper (TH) cells and altered adaptive immune responses. With TCDD, most adaptive immune responses are highly suppressed, which has been recently linked to the AHR-dependent induction of CD4+CD25+ regulatory T cells. However activation of AHR by certain non-TCDD ligands may result in other immune outcomes, as a result of metabolism of the ligand to active metabolites or to unknown ligand-specific effects on AHR-mediated gene transcription. Based on studies using AHR−/− mice, evidence for a role of endogenous AHR ligands in regulation of the immune response is growing, with bilirubin and lipoxinA4 representing two promising candidates.
登录
查看更多内容
DOI：
10.1016/0272-0590(90)90175-j
发表时间：
1990-07-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
BIRNBAUM, LS;MCDONALD, MM;HARRIS, MW
通讯作者：
HARRIS, MW
影响因子：
15.3
作者：
Herman, AE;Freeman, GJ;Benoist, C
通讯作者：
Benoist, C
DOI：
10.1073/pnas.88.21.9543
发表时间：
1991-11-01
影响因子：
11.1
作者：
BJELDANES, LF;KIM, JY;BRADFIELD, CA
通讯作者：
BRADFIELD, CA
DOI：
10.1016/s0192-0561(99)00053-3
发表时间：
1999-12-01
期刊：
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Hundeiker, C;Pineau, T;Esser, C
通讯作者：
Esser, C
影响因子：
12.8
作者：
Cheon, HyeonJoo;Woo, Young-Seok;Sohn, Jeongwon
通讯作者：
Sohn, Jeongwon