芳烃受体：关键信号伙伴及其在炎症性疾病中的免疫调节作用
Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases
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影响因子:5.9
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
DOI:
10.3389/fimmu.2024.1421346
摘要
芳烃受体（AhR）是一种多功能的环境感知和转录因子，遍布全身，响应来自环境、饮食、宿主微生物组及内源性代谢过程的多种小分子。越来越多的证据显示，AhR在调节细胞分化、免疫反应、新陈代谢甚至肿瘤形成等多种生物学功能中起关键作用。AhR通常位于细胞质中，激活后转移到细胞核，与芳烃受体核转录因子（ARNT）或低氧诱导因子1β（HIF-1β）结合，形成复合物，进而与异生物反应元件（XRE）结合调控关键基因的表达。AhR在多种重要免疫细胞中表达，近期研究强调其在先天免疫和获得性免疫中的重要影响。本文综述了AhR的结构、激活配体及其多方面作用，探讨AhR影响免疫与淋巴细胞的复杂分子通路，强调其在炎症性疾病中的新兴作用及潜在的靶向治疗策略，为免疫相关疾病的治疗开辟新途径。
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.