芳基烃受体：关键信号伴侣的当前观点和炎症性疾病中免疫调节作用
Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases
影响因子:5.90000
分区:医学2区 / 免疫学2区
发表日期:2024
作者:
Fatemah Bahman, Khubaib Choudhry, Fatema Al-Rashed, Fahd Al-Mulla, Sardar Sindhu, Rasheed Ahmad
摘要
芳基碳氢化合物受体（AHR）是整个人体中发现的多功能环境传感器和转录因子，对来自环境，饮食，宿主微生物组和内部代谢过程的广泛的小分子反应。越来越多的证据突显了AHR作为众多生物学功能的关键调节剂的作用，例如细胞分化，免疫反应，代谢甚至肿瘤形成。 AHR通常位于细胞质中，在激动剂激活后将其与芳基烃受体核转运剂（ARNT）或低氧诱导因子1β（HIF-1β）合作时移动到核。然后，该复合物与异种生物反应元件（XRES）相互作用，以控制关键基因的表达。 AHR明显存在于各种关键的免疫细胞中，最近的研究强调了其对先天和适应性免疫的显着影响。这篇评论深入研究了有关AHR结构，激活配体及其多面角色的最新见解。我们探索了AHR影响免疫和淋巴样细胞的复杂分子途径，强调了其在管理炎症性疾病中的重要重要性。此外，我们讨论了开发调节AHR活性的靶向疗法的令人兴奋的潜力，从而为免疫相关条件开辟了新的医疗干预途径。
Abstract
The aryl hydrocarbon receptor (AhR) is a versatile environmental sensor and transcription factor found throughout the body, responding to a wide range of small molecules originating from the environment, our diets, host microbiomes, and internal metabolic processes. Increasing evidence highlights AhR's role as a critical regulator of numerous biological functions, such as cellular differentiation, immune response, metabolism, and even tumor formation. Typically located in the cytoplasm, AhR moves to the nucleus upon activation by an agonist where it partners with either the aryl hydrocarbon receptor nuclear translocator (ARNT) or hypoxia-inducible factor 1β (HIF-1β). This complex then interacts with xenobiotic response elements (XREs) to control the expression of key genes. AhR is notably present in various crucial immune cells, and recent research underscores its significant impact on both innate and adaptive immunity. This review delves into the latest insights on AhR's structure, activating ligands, and its multifaceted roles. We explore the sophisticated molecular pathways through which AhR influences immune and lymphoid cells, emphasizing its emerging importance in managing inflammatory diseases. Furthermore, we discuss the exciting potential of developing targeted therapies that modulate AhR activity, opening new avenues for medical intervention in immune-related conditions.