Pilot: Center for Appalachian Research in Environmental Sciences: The Role of Oxidized Lipids and CD36 in PFOS-Induced Immunotoxicity

This proposal outlines a career development plan to help me establish an independent research program focused on the immunotoxicity of environmental pollutant. The essential components of my transition into research independence are mentored training in 1) mechanism study of immune effects using in vitro models; 2) design animal studies to assess immunotoxicity. My mentoring team will provide an outstanding training environment to fill critical gaps in my toolkit on in vivo/in vitro models and immunotoxicity studies. Perfluorooctane sulfonate (PFOS, an 8-carbon PFAS) is one of the environmental pollutants detected with high frequency and concentration in human and environmental samples. Research suggests that PFOS can induce immunotoxicity in spleen and alter responses of both the adaptive and innate immune systems. The rationale for my research project is that oxidized lipids and the scavenger receptor CD36 are central metabolic modulators of T cell metabolism in immune responses. However, the role of a CD36-oxidized lipid axis in PFOS exposure induced immunotoxicity hasn’t been explored. Based on my preliminary data presented in this application, my central hypothesis is that PFOS interferes with CD36 pathways and lipid metabolism in T cells, therefore resulting in immunotoxicity. The study will 1) determine the effects of PFOS on CD36-oxidized lipid axis in splenic T cells, and 2) delineate the gender differences in splenic T cell immunometabolism after PFOS exposure. The proposed studies will generate important data that open previously unappreciated links between lipid metabolism and immunotoxicity induced by PFOS exposure. Data from this study will lead to a successful future R01 submission to the Study Section of Systemic Injury by Environmental Exposure.