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STUDY QUESTION What role do female sex hormones play in the antisperm immune response?, SUMMARY ANSWER We found that sperm induce a Th17 immune response and that estradiol down-regulates the antisperm Th17 response by dendritic cells., WHAT IS KNOWN ALREADY Estradiol down-regulates the immune response to several pathogens and impairs the triggering of dendritic cell maturation by microbial products., STUDY DESIGN, SIZE, DURATION Ex vivo and in vivo murine models of vaginal infection with sperm and Candida albicans were used to study the induction of Th17 and its hormonal regulation., PARTICIPANTS/MATERIALS, SETTING, METHODS We analyzed the induction of Th17 cytokines and T cells in splenocytes obtained from BALB/c mice challenged with sperm and C. albicans. For the in vivo vaginal infection models, we used ovariectomized mice treated with vehicle, estradiol or progesterone, and we assessed the effect of these hormones on the immune response in the lymph nodes., MAIN RESULTS AND THE ROLE OF CHANCE Th17 cytokines and T cells were induced by sperm antigens in both ex vivo and in vivo experiments. Estrus levels of estradiol down-regulated the Th17 response to sperm and C. albicans in vivo., LIMITATIONS, REASONS FOR CAUTION This study was conducted using murine models; whether or not the results are applicable to humans is not known., WIDER IMPLICATIONS OF THE FINDINGS Our results describe an adaptive mechanism that reconciles immunity and reproduction and further explains why unregulated Th17 could be linked to infertility and recurrent infections.