Novel Roles for Immune Molecules in Brain Development and Disease

May 8, 2015, 11 a.m. to noon

A. Kimberley McAllister, PhD, Associate Professor, Center for Neuroscience, Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California Davis, Davis, California

Virginia Tech Carilion Research Institute, R3012

Recently, Dr. McAllister’s laboratory discovered that components of the immune system, including major histocompatibility class I (MHCI) molecules and several cytokines, are present in the healthy cerebral cortex where they negatively regulate the establishment of connections. In her discussion, she will review current models for MHCI function in neural development, focusing on a recent discovery from her laboratory of a novel MHCI signaling pathway in neurons that requires myocyte enhancer factor 2 (MEF2) transcription factors. Then, Dr. McAllister will describe how this MHCI-MEF2 signaling pathway mediates the effects of a mouse model of maternal immune activation (MIA), a risk factor for both ASD and SZ, on connectivity in offspring. She will present evidence consistent with a potential role for cytokines, especially interleukin-1β, in linking maternal infection to changes in neuronal levels of MHCI and connectivity. Together, these results suggest that both genetic associations and environmental risk factors for ASD and SZ that involve immune dysregulation may converge on a common cytokine-MHCI signaling pathway to regulate cortical connectivity and contribute to neurodevelopmental disorders.