2018 Frontiers in Immunology.pdf

Soluble CD83 (sCD83) is the extracellular domain of the membrane-bound CD83
molecule, and known for its immunoregulatory functions. Whether and how sCD83
participates in the pathogenesis of uveitis, a serious inflammatory disease of the eye that
can cause visual disability and blindness, is unknown. By flow cytometry and imaging
studies, we show that sCD83 alleviates experimental autoimmune uveitis (EAU) through
a novel mechanism. During onset and recovery of EAU, the level of sCD83 rises in the
serum and aqueous humor, and CD83+ leukocytes infiltrate the inflamed eye. Systemic
or topical application of sCD83 exerts a protective effect by decreasing inflammatory
cytokine expression, reducing ocular and splenic leukocyte including CD4+ T cells and
dendritic cells (DCs). Mechanistically, sCD83 induces tolerogenic DCs by decreasing the
synaptic expression of co-stimulatory molecules and hampering the calcium response
in DCs. These changes are caused by a disruption of the cytoskeletal rearrangements
at the DC–T cell contact zone, leading to altered localization of calcium microdomains
and suppressed T-cell activation. Thus, the ability of sCD83 to modulate DC-mediated
inflammation in the eye could be harnessed to develop new immunosuppressive therapeutics
for autoimmune uveitis.