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The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune-modulation and a delivery system capable of crossing the blood-brain-barrier. The recent identification and characterization of a small population of regulatory T (Treg) cells resident in the brain presents one such potential therapeutic target. Here we identified brain interleukin 2 (IL-2) levels as a limiting factor for brain-resident Treg cells. We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially direct delivery to inflammatory sites. Our results validate brain-specific IL-2 gene delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of diverse biologics to neuroinflammatory patients.
Prof. Adrian Liston is a senior group leader at the Babraham Institute in Cambridge. He is also a professor at the KU Leuven and head of the VIB Translational Immunology Laboratory. His main research interests are in the fields of neuroimmunology, autoimmunity, primary immune deficiencies and diabetes. Liston led the discovery of Pyrin-associated auto-inflammation with neutrophilic dermatosis, a previously unknown auto-inflammatory disease caused by mutation in the gene MEFV. Liston is also known for identifying genetic fragility of pancreatic beta cells as a cause of diabetes. Liston led a team that found that cohabitation modified the immune system, making partners more similar to each other. His research team has emphasized the role of the environment over genes in shaping the immune system. His team identified novel mutations in the gene STAT2 which lead to primary immunodeficiency.Liston also led a team that developed a machine learning algorithm that identifies children with juvenile arthritis with almost 90% accuracy from a simple blood test. In the neuroimmunology field he identified a role for white blood cells in the development of the brain.