Exposure Cessation During Adulthood Did Not Prevent Immunotoxicity Caused by Developmental Exposure to Low-Level Trichloroethylene in Drinking Water

Abstract

Exposure to the water pollutant trichloroethylene (TCE) can promote autoimmunity in both humans and rodents. Using a mouse model we have shown that chronic adult exposure to TCE at 500 μg/ml in drinking water generates autoimmune hepatitis in female MRL+/+ mice. There is increasing evidence that developmental exposure to certain chemicals can be more toxic than adult exposure. This study was designed to test whether exposure to a much lower level of TCE (0.05 μg/ml) during gestation, lactation, and early life generated autoimmunity similar to that found following adult exposure to higher concentrations of TCE. When female MRL+/+ mice were examined at postnatal day (PND) 259 we found that developmental/early life exposure [gestational day 0 to PND 154] to TCE at a concentration 10 000 fold lower than that shown to be effective for adult exposure triggered autoimmune hepatitis. This effect was observed despite exposure cessation at PND 154. In concordance with the liver pathology, female MRL+/+ exposed during development and early life to TCE (0.05 or 500 μg/ml) generated a range of antiliver antibodies detected by Western blotting. Expression of proinflammatory cytokines by CD4+ T cells was also similarly observed at PND 259 in the TCE-exposed mice regardless of concentration. Thus, exposure to TCE at approximately environmental levels from gestational day 0 to PND 154 generated tissue pathology and CD4+ T cell alterations that required higher concentrations if exposure was limited to adulthood. TCE exposure cessation at PND 154 did not prevent the immunotoxicity.

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

“…As shown by ourselves and others, TCE exposure increased the percentage of IFN-γ-and IL- More recently, our lab demonstrated that continuous exposure to levels of TCE described here was sufficient to promote autoimmune disease in female mice at PND259. Remarkably, the autoimmunity in the form of AIH tissue pathology and anti-liver antibodies was detected 15 weeks after exposure ended, indicating that removal of TCE does not prevent immune-mediated liver pathology (Gilbert et al, 2017).…”

“…More recently, our lab demonstrated that continuous exposure to levels of TCE described here was sufficient to promote autoimmune disease in female mice at PND259. Remarkably, the autoimmunity in the form of AIH tissue pathology and anti‐liver antibodies was detected 15 weeks after exposure ended, indicating that removal of TCE does not prevent immune‐mediated liver pathology (Gilbert et al, ). Given the correlation between gut dysbiosis and autoimmunity, our goal in the current study was to expand this research to assess the impact of developmental TCE exposure on the gut microbiome and gut‐associated immune responses.…”

“…We and others have shown the effect of continuous developmental exposure to TCE in mice encompassing gestation, lactation, and early life generated CD4 + T‐cell alterations and/or early signs of tissue inflammation in both normal and autoimmune‐susceptible mouse strains (Blossom, Melnyk, Li, Wessinger, & Cooney, ; Gilbert, Woodruff, & Blossom, ; Peden‐Adams et al, ; Peden‐Adams et al, ). We recently reported that continuous developmental exposure to TCE beginning at gestation generated autoimmune hepatitis (AIH)‐like tissue pathology at postnatal day (PND) 259 even when TCE was removed from the drinking water at PND154 (Gilbert, Bai, Barnette, & Blossom, ).…”

“…We recently reported that continuous developmental exposure to TCE beginning at gestation generated autoimmune hepatitis (AIH)-like tissue pathology at postnatal day (PND) 259 even when TCE was removed from the drinking water at PND154 (Gilbert, Bai, Barnette, & Blossom, 2017).…”

Environmental cues received during development shape dendritic cell responses later in life

“…For instance, reports from human population studies show that prenatal and early postnatal exposure to certain pollutants correlates with immune dysregulation later in life [ 1 – 4 ]. Research in animal models further supports the idea that immune function at maturity is influenced by early life exposures [ 5 – 9 ], and that the developing immune system is more sensitive than the mature immune system to enduring modulation by environmental factors [ 10 – 12 ]. While these studies reveal links between developmental exposures and life-long changes in immune function, how early life exposures shape the immune system is not fully understood.…”