CD83⁺ B cells alleviate uveitis through inhibiting DCs by sCD83

Soluble CD83 (sCD83) exerts immunosuppressive functions in many autoimmune diseases, including experimental autoimmune uveitis (EAU), but the cells and mechanisms involved are unclear. This study showed that CD83⁺ B cells were the main sources of sCD83. They alleviated the symptoms of EAU and decreased the percentage of T cells and DCs in the eyes and lymph nodes. These CD83⁺ B cells decreased IL-1β, IL-18 and IFN-γ secretion by DCs through sCD83. sCD83 interacted with GTPase Ras-related protein (Rab1a) in DCs to promote Rab1a accumulation in autolysosomes and inhibit mTORC1 phosphorylation and NLRP3 expression. Hence, CD83⁺ B cells play a regulatory role in EAU by secreting sCD83. The lack of regulation of CD83⁺ B cells might be an important factor leading to hyperimmune activation in patients with autoimmune uveitis. CD83⁺ B cells suppress activated DCs in uveitis, indicating the potential therapeutic role of CD83⁺ B cells in uveitis.