The overall goal of our multi-disciplinary Program Project is to understand the mucosal immune system in the human reproductive tract (FRT). The Program Project brings together endocrinologists and immunologists to characterize epithelial cell, myeloid cell and lymphocyte functions in the reproductive tract and obtain an integrated understanding of endocrine and cytokine control of the mucosal immune system in FRT. Our overall hypothesis is that the FRT is fully immunocompetent, and is regulated throughout the menstrual cycle and following menopause by sex hormones, cytokines and growth factors. The proposed studies focus on the presence and function of immune cells in reproductive tract issues from women undergoing hysterectomy. Sex hormone and cytokine regulation of reproductive architecture, antigen presentation, and myeloid cell and lymphocyte function will be investigated to obtain an integrated understanding of mucosal immune function in the Fallopian tube, uterus, cervix and vagina. Support the for 3 research projects will provided by 3 cores: Administrative, Tissue Procurement and Technical Support. The first Project will determine whether immune cell organization in the FRT varies with the stage of menstrual cycle and menopause. We will test the hypothesis that steroid hormones and cytokines differentially regulate the organization and function of immune cells with microenvironments of FRT tissues. The second Project will assess the inductive arm of the mucosal immune system in the FRT. The hypothesis to be tested is that epithelial cells, macrophages, dendritic cells and B cells throughout the FRT present antigen. We will assess how antigen presentation is influenced by endocrine balance and whether FRT antigen presentation can be enhanced by receptor (pIgR and FcR) targeting. The third project will define the response arm of the mucosal immune system in the FRT. The hypothesis to be tested is that lymphocytes provide protection against pathogens while maintain reproductive function. These studies will determine whether selective loss of CTL function in the uterus during the secretory phase of the menstrual cycle is down-regulated by FRT leukocytes. These studies will increase our presently limited understanding of immune protection of the female reproductive tract and should provide the basis of knowledge essential for the prevention of local infection in the genital mucosa, the management of sexually transmitted diseases, and insight into the heterosexual transmission of HIV-1.
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