Division of Neurology, Geneva University Hospital and Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Swiss Med Wkly. 2012 May 31;142:w13592. doi: 10.4414/smw.2012.13592. eCollection 2012.
The ligand activated transcription factor aryl hydrocarbon receptor (AhR) has been studied for many decades in toxicology as the ligand for the environmental contaminant dioxin. However, AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems, and several AhR ligands with different pharmacological profiles have recently been studied. The current review discusses new insights into the role of AhR signalling and AhR ligands on the regulation of the immune system, with a focus on regulatory T cells which maintain immune tolerance. Notably, AhR is expressed and modulates the development of two induced regulatory CD4+ T cell subsets, the forkhead box P3-positive (Foxp3+) regulatory T cells (iTreg) and the IL-10-secreting type 1 regulatory T (T(R)1) cells, through different signalling pathways. We will finally discuss how AhR ligands could be exploited to alleviate human autoimmune diseases. Clearly, drugs targeted against AhR should promote the development of new strategies to fight against autoimmune diseases.
配体激活的转录因子芳香烃受体 (AhR) 在毒理学中已被研究了数十年，它是环境污染物二恶英的配体。然而，AhR 最近已成为影响先天和适应性免疫系统的免疫反应的关键生理调节剂，并且最近已经研究了几种具有不同药理学特征的 AhR 配体。本综述讨论了关于 AhR 信号转导和 AhR 配体在免疫系统调节中的新见解，重点是维持免疫耐受的调节性 T 细胞。值得注意的是，AhR 通过不同的信号通路表达并调节两种诱导的调节性 CD4+T 细胞亚群的发育，叉头框 P3 阳性 (Foxp3+)调节性 T 细胞 (iTreg) 和白细胞介素-10 分泌型 1 调节性 T (T(R)1) 细胞。最后，我们将讨论 AhR 配体如何被利用来减轻人类自身免疫性疾病。显然，针对 AhR 的药物应该促进开发新的策略来对抗自身免疫性疾病。
