Tumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Tumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Trends Immunol. 2018 Dec;39(12):1005-1020. doi: 10.1016/j.it.2018.10.010. Epub 2018 Nov 5.
The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor and transcription factor activated through cognate ligand binding. It is an important factor in immunity and tissue homeostasis, and structurally diverse compounds from the environment, diet, microbiome, and host metabolism can induce AhR activity. Emerging evidence suggests that AhR is a key sensor allowing immune cells to adapt to environmental conditions and changes in AhR activity have been associated with autoimmune disorders and cancer. Furthermore, AhR agonists or antagonists can impact immune disease outcomes identifying AhR as a potentially actionable target for immunotherapy. In this review, we describe known ligands stimulating AhR activity, downstream proinflammatory and suppressive mechanisms potentiated by AhR, and how this understanding is being applied to immunopathology to help control disease outcomes.
芳香烃受体 (AhR) 是一种细胞质受体和转录因子,通过同源配体结合而被激活。它是免疫和组织动态平衡的重要因素,环境、饮食、微生物组和宿主代谢中的结构多样的化合物可以诱导 AhR 活性。新出现的证据表明,AhR 是允许免疫细胞适应环境条件的关键传感器,AhR 活性的变化与自身免疫性疾病和癌症有关。此外,AhR 激动剂或拮抗剂可以影响免疫性疾病的结果,这表明 AhR 是免疫治疗的一个潜在作用靶点。在这篇综述中,我们描述了已知的刺激 AhR 活性的配体、AhR 增强的下游促炎和抑制机制,以及如何将这一认识应用于免疫病理学以帮助控制疾病结果。