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AIM: To examine if estrogen can affect the immune response at the dendritic cells (DCs) level in rats with experimental autoimmune encephalomyelitis (EAE). METHODS: Lewis rats were immunized with inoculum containing MBP68-86. DCs were derived from spleen monocytes of EAE rats with IL-4 and GM-CSF in presence of 17β-estradiol (E2). Nitric oxide (NO) was detected by Griess reagent. The surface markers and cytokines production of DCs were shown by flow cytometry. DCs were cocultured with MBP-specific T cells, [3H]-TdR incoportation was used to reveal the antigen presentability, the supematant of the coculture were collected to examine the cytokines secretion by ELISA. RESULTS: E2 activated DCs by accelerating the maturation process characterized by upregulation of MHC II and costimulating molecule B7-1, B7-2, drastic high expression of CD40. IFN-γ-producing DCs were also elevated without any alteration of IL-10. Estradiol-treated DCs (E2-DCs) secreted more NO in the culture supeatant. By contrast, E2-DCs showed decreased antigen presentation ability with reduced secretion of IFN-γ but no alteration of IL-10 in the coculture with T cells. CONCLUSION: Estrogen can affect the differentiation, maturation and function of DCs from EAE rats, which may be attributed to its protection against EAE and the remission of multiple sclerosis patients in pregnancy.