“Microbiome-immune crosstalk in neurodevelopmental disease”
Dr. John Lukens is an Assistant Professor at the University of Virginia. His research aims to understand how immunologic pathways and interactions contribute to neurodevelopmental diseases. During his talk, he focused on his lab’s work related to the microbiome-immune crosstalk influencing autism and multiple sclerosis. Significant research exists implicating the microbiome in the pathogenesis of autism spectrum disorders. Dr. Lukens and his team found that microbiome differences between Jackson and Taconic mice change the TH17 response and the expression of an autistic phenotype. Further, they showed microbiota transfer of the maternal microbiome of susceptible, Taconic mice induces autism susceptibility in Jackson mice. They then asked what metabolites are affected by changes in the microbiome. They found that Taconic dam’s injected with Poly-IC have increased IL-17a compared to Jackson mice. Inhibiting IL-17 in pregnant dams rescued the mice from an autistic phenotype. Further work will investigate additional metabolic mediators and identify protective commensal bacteria. Dr. Lukens then shared his work on inflammasome biology, specifically with relation to experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. Caspase 1 in inflammasomes is thought to be required to cleave IL-1β into active IL-1. However, research from the Lukens lab suggests inflammasome-independent cleavage of IL-1 is important in driving EAE. They found that reduced levels of IL-1 receptor correlate with a reduced disease burden; knocking out caspase 1 does not confer protection, but knocking out the IL-1 receptor does. Further research will seek to better define the pathways and pharmaceutical targets involved in this phenomenon.
Check out Dr. Lukens’s work here: Lukens Lab