Vaccination with circulating exosomes in autoimmune uveitis prevents recurrent intraocular inflammation

Abstract

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 histological features of pan uveitis in man, we evaluated the immunoregulatory function of circulating exosomes. Methods Experimental autoimmune uveitis was induced in Lewis rats either immunised 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 immunised Lewis rats. The effect of exosomes on specific T cells was evaluated by R16‐specific T cell proliferation, cytokine production and recurrent uveitis induction. Results Circulating exosomes derived from active immunised 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‐γ production and increased IL‐10 after vaccination. Conclusions Circulating exosomes in autoimmune uveitis have the potential to be a novel treatment for recurrent autoimmune uveitis.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

“…228−230 Circulating exosomes from immunized uveitis mice could also induce suppressive effects on immune cells when transferred to naive mice. 231 Rapamycin, an immunosuppressive drug, when loaded in the MSC-derived EVs, produced an enhanced inhibitory effect on uveitis-related autoreactive T cells compared with the pharmacological treatment alone, thus establishing the role of EVs in the targeted delivery and cure. 232 3.4.3.…”

Salivary Exosomes in Health and Disease: Future Prospects in the Eye

“…The biomarkers that are transported by MSC-derived exosomes have exhibited mainly anti-inflammatory effects in diabetic retinopathy [ 279 , 280 , 281 ] and corneal disease [ 308 , 309 , 314 ], similar to the effects of MSC-derived exosomes in non-ocular diseases. In contrast, the biomarkers of other exosome types, such as serum-derived exosomes, have been revealed to both alleviate and exacerbate ocular disease pathogenesis [ 302 , 326 , 332 ].…”

“…After EAU was induced in mice, a treatment with the IL-35 exosomes resulted in the proliferation of IL-10- and IL-35-secreting T regulatory cells and the attenuation of Th17 responses, while marked choroiditis and photoreceptor cell death were seen in the control mouse eyes [ 325 ]. Even more recently, Jiang et al examined the immunomodulatory role of circulating exosomes that were derived from uveitis rats that had been immunized with interphotoreceptor retinoid-binding protein R16 [ 326 ]. The treatment of non-immunized uveitis rats with these circulating exosomes blunted the inflammatory responses of the R16-specific T cells, as evidenced by a reduced IFN-γ and increased IL-10 production [ 326 ].…”

“…Even more recently, Jiang et al examined the immunomodulatory role of circulating exosomes that were derived from uveitis rats that had been immunized with interphotoreceptor retinoid-binding protein R16 [ 326 ]. The treatment of non-immunized uveitis rats with these circulating exosomes blunted the inflammatory responses of the R16-specific T cells, as evidenced by a reduced IFN-γ and increased IL-10 production [ 326 ].…”

Extracellular Vesicles as Biomarkers and Therapeutics for Inflammatory Eye Diseases

“…Compared with normal MSC-derived EVs, IL-10 EVs suppressed proliferation and differentiation of Th1 and Th17 cells more effectively, ameliorating EAU better than normal MSC-derived EVs. Interestingly, in a separate study, EVs isolated from the blood of EAU Lewis rats induced with interphotoreceptor retinoid-binding protein (IRBP) R16 have also shown therapeutic properties in uveitis,176 with EVs isolated from EAU rats inhibiting the immune responses of R16 specific T-cells in vitro. When control Lewis rats were injected with the EAU-derived EVs and subsequently induced with EAU, the severity of EAU was significantly reduced with lower levels of IFN-γ and increased levels of IL-10.…”