![]() Naïve T-cells are produced by the thymus and, after release, are activated in secondary lymphoid tissues when they encounter antigen-presenting cells. Additionally in vitro and in vivo studies demonstrate altered expression of cytokines in response to uranium exposure which may lead to changes in T-cell ratios. Decreased natural killer and T-lymphocyte absolute counts were seen in people living near a uranium mine and displaying high uranium blood levels. However, people with a high lifetime exposure to uranium were shown to have decreased white blood cell and lymphocyte counts and increased eosinophil counts indicating immune dysregulation. Less is known about uranium and effects on immune function. Arsenic is able to modify cytokine production in response to T-cell activation possibly altering the ratio of T-cell populations. A variety of studies, including in vitro, animal and population studies, reveal that exposure to metals may induce immune dysregulation through altered expression of key immune regulators, oxidative stress, induced apoptosis, and impaired lymphocyte activation and function, ,, , ]. Additionally, uranium consumption through drinking water is associated with increased detection of autoantibodies to native DNA and/or chromatin. Studies have shown that populations living near AUMs have an increased likelihood of developing multiple chronic diseases, ,, ]. Health consequences such as increased risk of cancer, cardiovascular disease, inflammation and immune dysregulation have been associated with environmental exposure to metals such as arsenic and uranium, ,, ]. population supporting increased exposure based on location. Populations living in close proximity to AUMs have higher levels of urinary metals, including uranium, compared to the general U.S. Surface waters near the Jackpile uranium mine in Laguna Pueblo have measured uranium as high as 772 ug/L. In the Southwest, a significant portion of the population relies on unregulated water sources, leaving these individuals vulnerable to arsenic and uranium exposures. Uranium and arsenic frequently co-occur in water sources in the Western US and unregulated water sources close to AUMs show the two metals can co-occur at levels that each metal may exceed the highest level of a contaminant that is allowed in drinking water or the US EPA maximum contamination limit, ,, , ]. Individuals living in close proximity to AUMs are at risk of exposure to heavy metal contaminants found in and around these sites. ![]() The results demonstrate the need to investigate metal and metalloid mixtures at environmentally relevant concentrations to better understand the toxicological impact of these mixtures on T-cell activation, function and immune dysregulation.Ībandoned uranium mines (AUMs) are scattered across the western region of the United States. ![]() While uranyl acetate alone did not significantly alter activation associated gene expression, the mixture of uranyl acetate with sodium arsenite demonstrated a combined effect relative to sodium arsenite alone. Increases in oxidative stress gene expression were observed with both sodium arsenite doses. Sodium arsenite induced a dose dependent effect on activation associated gene expression targeting immune response genes at the lower dose. To address the potential effect of these metals on the activation of CD4+ T-cells, we used RNA sequencing methods to determine the effect of exposure to sodium arsenite (1 μM and 10 μM), uranyl acetate (3 μM and 30 μM) or a mixture of sodium arsenite and uranyl acetate (1 μM sodium arsenite + 3 μM uranyl acetate). Metals including arsenic and uranium co-occur in and around these sites at levels higher than the United States Environmental Protection Agency maximum contaminant levels. Communities in the western region of the United States experience environmental exposure to metal mixtures from living in proximity to numerous unremediated abandoned uranium mines.
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