Vaccination with circulating exosomes in autoimmune uveitis prevents recurrent intraocular inflammation

Background

Exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including autoimmune development. The role of circulating exosomes in the development of autoimmune uveitis is unknown. In this study, using the rat model of experimental autoimmune uveitis which has clinical and histologic features of pan uveitis in man, we evaluated the immunoregulatory function of circulating exosomes.

Methods

Experimental autoimmune uveitis was induced in Lewis rats either immunized with interphotoreceptor retinoid-binding protein R16 peptides or injected with activated R16-specific T cells. The disease incidence and severity were examined by indirect fundoscopy and flow cytometry. Circulating exosomes were isolated from peripheral blood of naïve and day 14 R16 immunized Lewis rats. The effect of exosomes on specific T cells were evaluated by R16-specific T cell proliferation, cytokine production and recurrent uveitis induction.

Results

Circulating exosomes derived from active immunized uveitis rats selectively inhibited immune responses of R16-specific T cells in vitro. Vaccination of naïve rats with these exosomes reduced the incidence of recurrent uveitis in an antigen specific manner. Antigen specific uveitogenic T cells reduced IFN- production and increased IL-10 after vaccination.

Conclusion

Circulating exosomes in autoimmune uveitis have the potential to be a novel treatment for recurrent autoimmune uveitis.

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