“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
Speaker: Dr. Anthony Blikslager, DVM, PhD, DACVS, from NC State
Title: “Do enteric glial cells play a role in age dependent mucosal repair?”
Summary: Dr. Anthony Blikslager is a Professor of Equine Surgery and Gastroenterology at NC State University. His lab’s focus is gastrointestinal physiology, specifically studying repair of the intestinal barrier and its role in healing in diseases like strangulating obstruction in animals and necrotizing enterocolitis in human newborns. In studying this intestinal barrier, Dr. Blikslager and his team found that prostaglandins stimulate the recovery of tight junctions in injured juvenile intestine. In the presence of a prostaglandin inhibitor, epithelial cells can repair but the tight junctions cannot, resulting in a leaky barrier. They also found an age dependence in barrier repair; younger mammals have greater difficult repairing their intestinal barrier. In newborns, epithelial restitution is arrested after ischemic injury. Using scanning electron microscopy, they have observed a different morphology in newborn and juvenile epithelial tissue. Neonatal epithelial tissue is rounded whereas juvenile tissue flattens out. The reason behind this remains unknown. To help answer this question, the lab has started to investigate the role of enteric glial cells in the healing process. They hypothesize that glial cells signal epithelial restitution. Further, they hypothesize that oligosaccharides feed the microbiota which in turns signals glial cells to support this restitution. Initial studies suggest that the enteric glial cell network is underdeveloped in neonates. Additionally, data show that feeding oligosaccharides results in both a maturation of the enteric glial cell network and a positive shift in the microbiome. These preliminary results suggest a temporal link to development of enteric glial cells, and define them as a potential target in intestinal barrier repair.