Linking PFAS exposure to thyroid disruption and innate immunity

PROJECT ABSTRACT
Per- and polyfluoroalkyl substances (PFASs) can be detected in the serum of 98% of Americans and have been
linked to several severe health effects, including cancer and inflammatory diseases. Many of these health effects
are linked to dysregulation of innate immune function, but how PFASs impact innate immunology is widely
unknown. Preliminary data show that PFAS exposure suppresses innate immune function in vitro and in vivo.
Further, PFAS exposure is associated with thyroid disease, and normal thyroid hormone levels are essential for
innate immune function. Therefore, the central hypothesis is that PFAS-induced immunotoxicity is mediated by
decreased thyroid hormone signaling. This hypothesis will be tested for multiple structurally diverse PFASs in
both human innate immune cell lines and a hypothyroid zebrafish model. Aim 1 will determine if PFAS-induced
suppression of natural killer (NK) cell function requires thyroid hormone signaling in vitro. Aim 2 will determine if
PFAS-induced suppression of phagocyte cell function requires thyroid hormone signaling in vivo and in vitro.
This work will begin to fill the knowledge gap surrounding PFAS-induced toxicity, specifically as it relates to their
immunotoxicity and their potential mechanisms of action. Successful completion of this project will inform hazard
identification and risk assessment processes and may lead to improved regulation of PFASs in the environment.