Immunoregulatory effects of Mesenchymal Stem Cells-Derived Exsomes in a Rabbit Model of Autoimmune Dacryoadenitis

Abstract

Abstract We previously demonstrated that mesenchymal stem cells (MSCs) ameliorated autoimmune dacryoadenitis in rabbits. Recently, MSC-derived exsomes (MSC-Exo) were considered to carry functions of MSCs. In this study, we investigated the effect of local administration of human MSC-Exo on rabbit autoimmune dacryoadenitis. Diseased rabbits were treated with MSC-Exo or PBS via subconjunctival injection on days 1, 3, 5, 7 and 9 after infusions of activated autologous lymphocytes, and clinical scores were determined by assessing tear production, break-up time and fluorescein. The in vitro effects of MSC-Exo on activated peripheral blood mononuclear cells (PBMCs) were determined by BrdU proliferation assay and Q-PCR assessing the mRNA expression levels of T cell or macrophage related cytokine genes and subpopulation-related marker genes. We found that subconjunctivally administered MSC-Exo greatly reduced the severity of autoimmune dacryoadenitis as their parent cells by reducing the infiltration of T cell subsets and other inflammatory-related factors in lacrimal glands. In vitro, the proliferation of autoreactive T cells was inhibited by MSC-Exo in a dose-dependent manner. MSC-Exo treatment significantly down-regulated the expression of M1 macrophage-related gene, while promoted the expression of anti-inflammatory M2 macrophage related genes. These results suggests that MSC-Exo effectively ameliorated autoimmune dacryoadenitis partially by inducing the generation of M2 macrophage, indicating a potential novel therapy of MSC-Exo for autoimmune dacryoadenitis.