IL-7: AhR We Ready for a New Cytokine to Fight Colitis?
IL-7: AhR We Ready for a New Cytokine to Fight Colitis?
复制标题
DOI：
10.1007/s10620-015-3721-x
复制
发表时间：
2015-05
影响因子：
3.1
通讯作者：
A. Nakao
中科院分区：
文献类型：
--
作者：
A. Nakao
芳基烃受体（AhR）是一种配体激活的转录因子，在脊椎动物细胞中普遍表达。 AhR 可识别人造合成化合物，例如 2,3,7,8-四氯二苯并-对二恶英（TCDD，二恶英）和天然存在的化合物，例如存在于十字花科蔬菜中的色氨酸衍生物吲哚-3-甲醇 (I3C)； AhR 被认为参与这些化合物的代谢或解毒 [1]。配体结合后，AhR 从胞质溶胶转位到细胞核，与芳烃受体核转位子 (AhRNT) 形成二聚体，并使用含有异生素响应元件 (XRE) 共有序列的启动子启动靶基因的转录。该通路的靶标包括编码外源代谢酶的基因，包括细胞色素 P450 家族 1A1 (CYP1A1)。AhR 通路不仅在人造和天然化学物质的代谢中发挥作用，而且还调节多种生理过程 [2]。特别是，该途径作为肠道粘膜免疫的重要调节剂[3]。值得注意的是，越来越多的证据表明 AhR 的激活对小鼠和人类的结肠炎有益 [4]。例如，用 TCDD 或 AhR 激动剂 6-甲酰吲哚 (3, 2-b) 咔唑 (FICZ) 治疗可保护小鼠免受葡聚糖硫酸钠 (DSS) 诱导的结肠炎 [5, 6]。在人类中，肠道 T 细胞和
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor ubiquitously expressed in vertebrate cells. AhR recognizes man-made synthetic compounds such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and naturally occurring compounds such as the tryptophan derivative indole-3-carbinol (I3C), which is present in cruciferous vegetables; AhR is thought to be involved in the metabolism or detoxification of these compounds [1]. Upon ligand binding, AhR translocates from the cytosol to the nucleus, dimerizes with the aryl hydrocarbon receptor nuclear translocator (AhRNT), and initiates the transcription of target genes with promoters containing the xenobiotic-responsive element (XRE) consensus sequence. The targets of this pathway include genes that encode xenobiotic-metabolizing enzymes, including cytochrome P450 family 1A1 (CYP1A1).The AhR pathway not only functions in the metabolism of man-made and naturally occurring chemicals, but also regulates a variety of physiological processes [2]. In particular, this pathway acts as a crucial regulator of mucosal immunity in the gut [3]. Notably, there is accumulating evidence that activation of AhR is beneficial for colitis in mice and humans [4]. For instance, treatment with TCDD or AhR agonist 6-formylindolo (3, 2-b) carbazole (FICZ) protects mice against dextran sulfate sodium (DSS)-induced colitis [5, 6]. In humans, intestinal T cells and