TCDD: An Environmental Immunotoxicant Reveals a Novel Pathway of Immunoregulation—A 30-Year Odyssey

Abstract

I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium “Toxicologic Pathology and the Immune System.” I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my research career that has spanned the past 40 years as well. An initial focus on the immunotoxicity of pentachlorophenol led my laboratory into the aryl hydrocarbon receptor (AHR) field and the study of its most potent ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). My research career has been devoted to trying to elucidate the immunological basis of TCDD’s profound immunosuppressive activity that is mediated by activation of AHR. In recent years, my laboratory has focused on the role of CD4+ T cells as targets of TCDD, and we were the first to describe the induction of AHR-dependent regulatory T cells (Tregs). The ability to induce Tregs using an exogenous AHR ligand to activate the AHR-Treg pathway represents a novel approach to the prevention and/or treatment of autoimmune disease. We are currently searching for such ligands.