I-a^lowCD11b^high DC Regulates the Immune Response in the Eyes of Experimental Autoimmune Uveitis

Regulatory dendritic cells (DC_reg) have been reported to be a negative regulator in the immune response. These cells are widely distributed in the liver, spleen, and lung. However, the status and function of DC_reg in the eyes and disease are still not very clear. Herein, we found that the number of I-a^lowCD11b^high DC increased in the eye and spleen at the recovery stage of experimental autoimmune uveitis (EAU), which is a mouse model for autoimmune uveitis. These cells expressed lower levels of CD80, CD86, and CD54 than the mature DCs and expressed interleukin 10 (IL-10), indoleamine 2,3-dioxygenase (IDO), and transforming growth factor beta (TGF-β) as well. Moreover, these DC_reg can regulate the development of EAU by promoting CD4⁺CD25⁺Foxp3⁺ regulatory T cells. The increased interferon-gamma (IFN-γ) in the aqueous humor of EAU participates in inducing DC_reg to alleviate the symptom of EAU. Furthermore, DC_reg was found to exist in the eyes of normal mice. Aqueous humor, containing a certain concentration of IL-10, TGF-β, prostaglandin E2 (PGE2), IDO, and nitric oxide (NO), induced the tolerance of DC_reg in normal eyes. It can be concluded that DC_reg exists in the eyes and plays a protective role in inflamed eyes. These DC_reg induced by IFN-γ might be used as a strategy to develop therapy for EAU management.