Do the monocyte-derived dendritic cells exert a pivotal role in the early onset of experimental autoimmune uveitis?

Abstract

Background: Eyes are recognized as immunological privileged site. However, the onset of autoimmune uveitis (AU) prompts an influx of dendritic cells (DCs) into the retinas, tasked with presenting auto-antigens, thereby exacerbating the inflammatory response. Monocyte-derived DCs (moDCs) implicated in various autoimmune disorders, but their specific involvement in AU remains unclear. This study aims to investigate the constitution and dynamics of retinal DCs subsequent to the induction of experimental autoimmune uveitis (EAU).

Methods: In our study, an EAU model was established in C57BL/6J mice, and prednisolone acetate (PA) eye drops were administrated unilaterally to the right eye from 5 days post-immunization (dpi). The infiltration of Gr-1⁺CD115⁺CD11c^-MHC-II^- cells (monocytes), Gr-1⁺CD115⁺CD11c⁺MHC-II⁺ cells (moDCs) and Gr-1^-CD115^-CD11c⁺MHC-II⁺ cells (conventional dendritic cells, cDCs) within retina were detected by flow cytometry and immunofluorescence stain at 7, 10, 13, and 16 dpi. Additionally, the protein expression and mRNA expression of pivotal cytokines associated with moDCs and inflammation were analysed by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively.

Results: Our findings unveiled a notable rise in moDCs infiltration and differentiation from 7 to 13 dpi. The administration of PA eye drops did not yield a significant variance in either the quantity or the differentiation rate of moDCs. Throughout the initial stages of EAU, the expression of GM-CSF remained consistent, while TGF-β1 exhibited a sustained increase until 13 dpi in the control group and until 10 dpi following PA treatment. Anti-inflammatory cytokines Il-10 and Il-4 displayed no significant increase until 16 dpi after PA administration.

Conclusions: Our results indicate that moDCs exhibited an earlier and more substantial infiltration into the inflamed retina compared to cDCs. This heightened presence of moDCs appeared to play a dominant role in the presentation of auto-antigens during the initial stages of EAU, consequently contributing to the exaggerated autoimmune response within the ocular milieu. The administration of PA exhibited no discernible impact on either the differentiation or the infiltration of moDCs.