2018 Frontiers in Immunology.pdf

2019-03-04T18:58:17Z (GMT) by Zhichao Fan
Soluble CD83 (sCD83) is the extracellular domain of the membrane-bound CD83<br>molecule, and known for its immunoregulatory functions. Whether and how sCD83<br>participates in the pathogenesis of uveitis, a serious inflammatory disease of the eye that<br>can cause visual disability and blindness, is unknown. By flow cytometry and imaging<br>studies, we show that sCD83 alleviates experimental autoimmune uveitis (EAU) through<br>a novel mechanism. During onset and recovery of EAU, the level of sCD83 rises in the<br>serum and aqueous humor, and CD83+ leukocytes infiltrate the inflamed eye. Systemic<br>or topical application of sCD83 exerts a protective effect by decreasing inflammatory<br>cytokine expression, reducing ocular and splenic leukocyte including CD4+ T cells and<br>dendritic cells (DCs). Mechanistically, sCD83 induces tolerogenic DCs by decreasing the<br>synaptic expression of co-stimulatory molecules and hampering the calcium response<br>in DCs. These changes are caused by a disruption of the cytoskeletal rearrangements<br>at the DC–T cell contact zone, leading to altered localization of calcium microdomains<br>and suppressed T-cell activation. Thus, the ability of sCD83 to modulate DC-mediated<br>inflammation in the eye could be harnessed to develop new immunosuppressive therapeutics<br>for autoimmune uveitis.