(112) showed that laquinimod, an oral drug currently being evaluated for treatment of relapsing and remitting MS, induced genes associated with the AHR pathway such as and in both naive and EAE mice treated with laquinimod and MOG-specific splenocyte assay (101). 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 exhibited 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 around 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 Guanosine 5′-diphosphate disodium salt 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 Guanosine 5′-diphosphate disodium salt providing the most up-to-date literature on the role Guanosine 5′-diphosphate disodium salt of AHR in autoreactive T cell function and autoimmune disease. is usually expressed in most CD4+ T cell subsets, with highest expression in T helper (Th)17, type 1 regulatory T cells (Tr1), forkhead box P3 (FOXP3)+ regulatory T cells (Treg), followed by Th1 and Th2 (44, 45) and is critical in modulating the balance between Th17 and Treg cells (44, 46). TCDD has been associated with an increase in Treg cells and immunosuppression, whereas other ligands such as 6-formylindolo[3,2-b] carbazole (FICZ), a tryptophan breakdown product, has been associated with enhanced Th17 effector cells and inflammation (44, 46). In the context of autoimmune disease, TCDD has been shown to enhance Treg differentiation and suppress experimental autoimmune encephalomyelitis (EAE), a murine model of autoimmune disease, and FICZ has been shown to enhance Th17 differentiation and worsen EAE (44, 46). This review summarizes the current research regarding the role of PM on development and/or progression of autoimmune disease. We first provide a brief overview of the role autoreactive T cells play in autoimmune diseases and summarize the evidence that PM impacts T cells and autoimmune disease. Given the numerous and extensive reviews on AHR ligands (40, 47), we only spotlight PM-mediated AHR effects and which has been associated with pathogenic events of autoimmune disease (59). Using cells from atopy-prone mice, which are highly sensitive hosts, Nakamura et CXCR2 al. (60) showed that nanoparticle-rich DEP reduced cell viability and proliferation in a dose-related manner. Retinoic-acid receptor-related orphan receptor gamma t (RORt) expression and subsequent IL-17A production/release by the cells was increased in the splenocytes in a dose-dependent manner implicating Th17 cells in PM-mediated immune responses. Additionally, CD4+ and CD8+ T cells exposed to PM2.5 significantly elevated mRNA and protein levels of inflammatory cytokine production in a macrophage-dependent manner (61). Furthermore, in a model of chronically inhaled PM2.5 for 24C28 weeks, exposure to PM2.5 resulted in increased T cell infiltration and increased activation of effector T cells in the lungs and indicates that PM2.5 potentiates a proinflammatory Th1 response (62). In addition, van Voorhis et al. (63) exhibited that a 3 day intranasal instillation of a standard reference material (SRM)1649b, an ambient urban dust PM sample, significantly upregulated IL-17 mRNA in the lung of C57BL/6 mice. Moreover, in a mixed leukocyte culture, using C57BL/6 splenocytes activated with Balb/c DCs, which creates an immune response, a significant increase in IL-17 protein was measured as well as IL-22 mRNA suggesting an increase in Th17 responses (63). Likewise, Castaneda et al. (64) exhibited that Guanosine 5′-diphosphate disodium salt PM enhances DC activation and primes na?ve T cell Guanosine 5′-diphosphate disodium salt differentiation toward a Th17-like phenotype and and EAE data using the intact PM and chemically-extracted OF, SRM1650b requires the particle to aggravate autoimmune disease because of bioavailability of the PAHs and their ability to activate the AHR. Like SRM1650b, SRM2975 enters the T cell, binds AHR, translocates to the nucleus, binds DNA, and drives transcription of CYP enzymes (bottom). However, SRM2975 enhances Th1 differentiation in an AHR-dependent manner but still worsens autoimmune disease (bottom). Based on the EAE data demonstrating SRM2975 worsens.
Home » Atrial Natriuretic Peptide Receptors » (112) showed that laquinimod, an oral drug currently being evaluated for treatment of relapsing and remitting MS, induced genes associated with the AHR pathway such as and in both naive and EAE mice treated with laquinimod and MOG-specific splenocyte assay (101)