Development of Immunologic therapies against uveitis

我们已经成功地从产生IL-35的布雷格细胞中分离出含有IL-35的外泌体（i35-外泌体），并使用它们来抑制患有后葡萄膜炎的小鼠视网膜中的自身反应性T细胞。用IL-35-外泌体处理的小鼠受到保护免于葡萄膜炎，并且不存在同种异体反应性或毒性使得135-外泌体成为将生物制剂递送至视网膜作为自身免疫性葡萄膜炎或年龄相关性黄斑变性（AMD）的治疗的有吸引力的治疗选择。我们还鉴定了组成型产生IL-27的独特B细胞群。这些B细胞在体内相对较少，但我们已经开发了一种离体测定，使我们能够产生大量的这种布雷格群体。我们现在正在研究i27-BAFR 4在EAU和EAE模型中的调节功能。在我们的初步研究中，我们已经从小鼠B细胞中分离出含有IL-27作为其主要货物的外泌体，并将检查它们是否可以抑制小鼠的葡萄膜炎。 我们还通过单细胞RNA-Seq（scRNA-Seq）、Chip-Seq和ATAC测序来表征IL-27-布雷格转录组。

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.