The role of estrogen in atrazine-mediated inhibition of CD4+ T cell function and induction of CD4+CD25+Foxp3+ regulatory T cells (IRC4P.479)

The herbicide Atrazine (ATR) is the most common drinking water contaminant in the US. Biochemically, ATR is a phosphodiesterase (PDE) inhibitor and also elevates estrogen via induction of aromatase. Based upon these biochemical activities and several previous studies, ATR is considered potentially immunotoxic. We have previously shown that when activated in the presence of ATR CD4+ T cell proliferation and expression of CD25 and CD69 are significantly reduced. This is accompanied by a 2-5 fold increase in the frequency of Foxp3+ CD25+ Treg. While this phenotype is partially mimicked by treatment with the PDE inhibitor pentoxifylline, the ATR phenotype is more pronounced in cells derived from male mice. This suggests the possibility that estrogen is playing an important role in the observed CD4+ T cell phenotype. To examine the potential role of estrogen in the ATR-associated phenotype, we have investigated the role of the G-protein coupled estrogen receptor, GPER1/GPR-30, in the ATR-mediated inhibition of CD4+ T cell activation and induction of Treg. Treatment with estrogen and the GPER1 agonist G1 mimic the effects of low ATR concentrations. Studies to further define the role of estrogen and GPER1 in the ATR inhibition of T cell activation and iTreg conversion are currently underway.