The Aryl Hydrocarbon Receptor as an Immune-Modulator of Atmospheric Particulate Matter-Mediated Autoimmunity

Abstract

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 in vitro and in vivo 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.

Environmental Stressors on Skin Aging. Mechanistic Insights

“…Some AhR ligands modulate the regulatory T cells differentiation or increase the proinflammatory differentiation of Th 17. Therefore, activation of AhR is critical in the increase of proinflammatory responses (O’Driscoll and Mezrich, 2018). In addition to the canonical AhR pathway, the activation of AhR often affects other signal transduction pathways, including NF-κB signals (Pollet et al, 2018).…”

A prospective pilot study of the T‐lymphocyte response to fine particulate matter exposure

“…AhR ligands adsorbed on the PM surface activate AhR leading to an upregulation of CYP enzymes. The extent and duration of the activation by the ligand can cause a shift in the immune response reducing or enhancing the effector T cells (O'Driscoll & Mezrich, ).…”

Cytochrome P4501B1 in bone marrow is co-expressed with key markers of mesenchymal stem cells. BMS2 cell line models PAH disruption of bone marrow niche development functions

“…PAHs produce diverse effects on the immune system, particularly on T-lymphocytes and dendritic cells (O'Driscoll et al, 2018;O'Driscoll and Mezrich, 2018). PAHs activate the AhR, which regulates the balance between effector and regulatory T cells (O'Driscoll and Mezrich, 2018) and induces CYP1A1 and CYP1B1.…”

“…In present times, we can also add the impact of smoking and environmental combustion pollutants on health outcomes from COVID-19 infection (Li Volti et al, 2020). The metabolism of these chemicals causes tissue injury and carcinogenic mutations (Bolton and Dunlap, 2017;Bostrom et al, 2002;Castano-Vinyals et al, 2004;Moorthy et al, 2015;Yang et al, 2019), and also impacts the immune system (O'Driscoll et al, 2018), notably from effects in the bone marrow (BM) (Larsen et al, 2016;N'Jai A et al, 2011;N'Jai A et al, 2010).…”