2-methoxyestradiol alleviates experimental autoimmune uveitis by inhibiting lymphocytes proliferation and T cell differentiation

Purpose. To investigate the effect of 2-Methoxyestradiol (2ME2) on experimental autoimmune uveitis (EAU) and the mechanism. Method. C57BL/6 male mice were used to establish the EAU model. 2ME2 was abdominal administrated in D0-D13, D0-D6, and D7-D13 and control group was given vehicle from D0-D13. At D14, pathological severity was scored. Lymphocyte reaction was measured using MTT assay. T cell differentiation in draining lymph nodes and eye-infiltrating cells was tested by flow cytometry. Proinflammatory cytokines production from lymphocytes was determined by ELISA. Result. The disease scores from 2ME2 D0-D13, 2ME2 D0-D6, 2ME2 D7-D13, and vehicle groups were 0.20±0.12, 1.42±0.24, 2.25±0.32, and 2.42±0.24. Cells from all 2ME2 treated groups responded weaker than control (p<0.05). The inhibitory effect of 2ME2 on lymphocyte proliferation attenuated from 2ME2 D0-D13 to 2ME2 D0-D6 and to 2ME2 D7-D13 groups (p<0.05). 2ME2 treated mice developed fewer Th1 and Th17 cells both in draining lymph nodes and in eyes than control (p<0.05). Lymphocytes from 2ME2 group secreted less IFN-γ and IL-17A than those from control (p<0.05). Conclusion. 2ME2 ameliorated EAU progression and presented a better effect at priming phase. The possible mechanism could be the inhibitory impact on IRBP specific lymphocyte proliferation and Th1 and Th17 cell differentiation.