Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.
Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.
Front Immunol. 2018 Dec 6;9:2833. doi: 10.3389/fimmu.2018.02833. eCollection 2018.
This review examines the current literature on the effects of atmospheric particulate matter (PM) on autoimmune disease and proposes a new role for the aryl hydrocarbon receptor (AHR) as a modulator of T cells in PM-mediated autoimmune disease. There is a significant body of literature regarding the strong epidemiologic correlations between PM exposures and worsened autoimmune diseases. Genetic predispositions account for 30% of all autoimmune disease leaving environmental factors as major contributors. Increases in incidence and prevalence of autoimmune disease have occurred concurrently with an increase in air pollution. Currently, atmospheric PM is considered to be the greatest environmental health risk worldwide. Atmospheric PM is a complex heterogeneous mixture composed of diverse adsorbed organic compounds such as polycyclic aromatic hydrocarbons (PAHs) and dioxins, among others. Exposure to atmospheric PM has been shown to aggravate several autoimmune diseases. Despite strong correlations between exposure to atmospheric PM and worsened autoimmune disease, the mechanisms underlying aggravated disease are largely unknown. The AHR is a ligand activated transcription factor that responds to endogenous and exogenous ligands including toxicants present in PM, such as PAHs and dioxins. A few studies have investigated the effects of atmospheric PM on AHR activation and immune function and demonstrated that atmospheric PM can activate the AHR, change cytokine expression, and alter T cell differentiation. Several studies have found that the AHR modulates the balance between regulatory and effector T cell functions and drives T cell differentiation and using murine models of autoimmune disease. However, there are very few studies on the role of AHR in PM-mediated autoimmune disease. The AHR plays a critical role in the balance of effector and regulatory T cells and in autoimmune disease. With increased incidence and prevalence of autoimmune disease occurring concurrently with increases in air pollution, potential mechanisms that drive inflammatory and exacerbated disease need to be elucidated. This review focuses on the AHR as a potential mechanistic target for modulating T cell responses associated with PM-mediated autoimmune disease providing the most up-to-date literature on the role of AHR in autoreactive T cell function and autoimmune disease.
这篇综述探讨了大气颗粒物（PM）对自身免疫性疾病的影响，并提出了芳烃受体（AHR）作为 PM 介导的自身免疫性疾病中 T 细胞调节剂的新作用。有大量文献表明，PM 暴露与自身免疫性疾病恶化之间存在很强的流行病学相关性。遗传易感性占所有自身免疫性疾病的 30%，而环境因素是主要原因。自身免疫性疾病的发病率和患病率增加与空气污染的增加同时发生。目前，大气 PM 被认为是全球最大的环境健康风险。大气 PM 是一种复杂的多相混合物，由多种吸附有机化合物组成，如多环芳烃（PAHs）和二恶英等。暴露于大气 PM 已被证明会加重几种自身免疫性疾病。尽管大气 PM 暴露与自身免疫性疾病恶化之间存在很强的相关性，但加重疾病的机制在很大程度上尚不清楚。AHR 是一种配体激活的转录因子，可响应内源性和外源性配体，包括 PM 中存在的有毒物质，如 PAHs 和二恶英。一些研究调查了大气 PM 对 AHR 激活和免疫功能的影响，结果表明大气 PM 可以激活 AHR，改变细胞因子表达，并改变 T 细胞分化。一些研究发现，AHR 调节调节性和效应性 T 细胞功能之间的平衡，并驱动 T 细胞分化[12,13]，使用自身免疫性疾病的小鼠模型。然而，关于 AHR 在 PM 介导的自身免疫性疾病中的作用的研究很少。AHR 在效应性和调节性 T 细胞的平衡以及自身免疫性疾病中起着关键作用。随着自身免疫性疾病的发病率和患病率的增加与空气污染的增加同时发生，需要阐明驱动炎症和加剧疾病的潜在机制。这篇综述重点介绍了 AHR 作为调节与 PM 介导的自身免疫性疾病相关的 T 细胞反应的潜在机制靶点，提供了关于 AHR 在自身反应性 T 细胞功能和自身免疫性疾病中的作用的最新文献。
