EXPOSURE TO A MIXTURE OF SUSPECTED THYROID DISRUPTING CHEMICALS ALTERS INTRATHYMIC T CELL DIFFERENTIATION IN XENOPUS LAEVIS TADPOLES
Connor McGuire, University of Rochester Medical Center
Authors: Connor C. McGuire1, Jacques Robert1, 2
1Department of Environmental Medicine, 2Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester NY.
Thyroid hormones (TH) control postembryonic vertebrate development through thyroid receptor (TR) signaling. Deficiencies in TH production during development are known to contribute to immunodeficiency in humans and poorer outcomes in autoimmune disease models. To investigate whether endocrine disrupting chemicals that act on the TH pathway can alter the development of the immune system, we have tested a mixture of chemicals used in unconventional oil and gas extraction that are suspected to be TR antagonists or TH synthesis inhibitors. We verified TR antagonist activity by exposing premetamorphic Xenopus laevis tadpoles to 1.25 nM of the TR agonist triido-L-thryonine (T3) and T3 combined with 1 μg/L or 10 μg/L of the mixture, and discovered that the 10 μg/L dose of the mixture prevented T3’s induction of the klf9 expression in the thymus, a key TR-responsive gene also critical for T cell development. To determine the effect of this
mixture on intrathymic T cell development at steady states, we exposed Xenopus laevis tadpoles to 1 μg/L or 10 μg/L of the mixture or DMSO control for two weeks and evaluated changes in thymocyte subsets using two-color flow cytometry. Exposure to the 10 μg/L dose of the mixture increased the number of CD8+, CD4+, double positive, and double negative thymocytes, while reducing a population of less well characterized CD8+/CD5- cells. Thus, our data suggest that disruption to the TH axis during tadpole development induces acute alterations to the thymus perturbating T cell differentiation.