Development of Immunologic therapies against uveitis

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We have successfully isolated exosomes that contain IL-35 (i35-Exosomes) from IL-35-producing Breg cells and used them to suppress autoreactive T cells in the retina of mice with posterior uveitis. Mice treated with IL-35-Exosomes were protected from uveitis and absence of alloreactivity or toxicity makes i35-Exosomes an attractive therapeutic option for delivering biologics to the retina as treatment for autoimmune uveitis or age-related macular degeneration (AMD). We have also identified a unique B cell population that constitutively produces IL-27. These B cells are relatively rare in-vivo but we have developed an ex-vivo assay that allows us to produce large amounts of this Breg population. We are now investigating regulatory functions of i27-Bregs in the EAU and EAE models. In our preliminary studies we have isolated exosomes that contain IL-27 as its major cargo from mouse B cells and will examine whether they can suppress uveitis in mice. We are also characterizing the IL-27-Breg transcriptome by single-cell RNA-Seq (scRNA-Seq), Chip-Seq and ATAC-Sequencing.