Discovery of Blood-Based Proteins That Mark Benzo[a]pyrene Modulation of Autoimmunity

Environmental pollutants are thought to shape our immune landscape and drive the rise in autoimmune disease incidence worldwide. However, the molecular underpinnings of environmental impact on autoimmunity remain elusive and a quantitative measurement for immune dysfunction as a result of environmental exposure is yet to be developed. To this end, we have performed a discovery study to identify blood-based, immune-associated proteins regulated by benzo[a]pyrene (BaP) using the autoimmune-prone murine model MRL. We report the upregulation of autoimmune-associated cytokines including IL1a and IFNg by BaP, months before the manifestation of autoimmune phenotypes. Additionally, the increased levels of proteins such as IL16, IL22 and SNCA in male MRL mice upon BaP exposure may be a molecular link to the increased risk in end organ damage in subsets of autoimmune disease patients. Further comparison with the transcriptomic analysis of BaP-stimulated skin and lungs suggests distinct patterns of immune regulation in peripheral organs versus blood. Altogether, our study supports the need for the early detection of BaP-induced immune changes for the prevention and management of autoimmune diseases and provides leads for the future development of these blood-based biomarkers.