Role of IL-12 family cytokines in human autoimmune Uveitis

National Eye Institute

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Abstract

In this study, we investigated mechanisms by which regulatory B cells (Bregs) suppress CNS autoimmune diseases such as Uveitis or Multiple Sclerosis. These studies focused on Bregs that secrete IL-10, IL-27 or IL-35. We have isolated these Breg cells from human PBMC, cord blood or bone marrow. We have successfully established protocols for sorting and purifying regulatory B cells that secrete IL-27 (i27-Breg) or IL-35 (i35-Breg. We have also established protocols for isolated IL-35 containing exosomes (i35-Exosome) from i35-Breg cells and IL-27 containing exosomes (i27-Exosome) from i27-Breg cells. Importantly, we have used the mouse derived i35-Exosome to suppress uveitis in mice, suggesting that i35-Exosomes can be developed as immunotherapy for CNS autoimmune and neurodegenerative diseases. We are now characterizing the Breg cells transcriptomes by single-cell RNA-Seq (scRNA-Seq), Chip-Seq, ATAC-Seq.