Neuronal GDF-15 delivery alters peripheral CD4+ T cell phenotype

In this study we investigated the immunomodulatory properties of GDF-15 in the context of neuroinflammation. We exploited neuronal gene therapy to overexpress GDF-15 within the central nervous system, which protected mice from developing any clinical signs of neuroinflammation in the experimental autoimmune encephalitis (EAE) model. We discovered that GDF-15 delivery modulated the peripheral T cell response and prevented immune cells from transmigrating into the central nervous system. Overall design: Female C57BL/6J mice were injected with an rAAV (PHP.eB) capsid to express eGFP or murine GDF-15 under the control of the human Synapsin 1 promoter to restrict expression to neurons. Three weeks later EAE was induced in half of the animals using MOG35-55/CFA and pertussis toxin. During the preclinical phase (day 9 post immunisation) EAE animals and healthy controls were sacrificed and spleens collected. CD4+ T cells were enriched using the MojoSort Mouse CD4 T Cell Isolation Kit.