Hormonal Modulation of DCs: Influences on Innate and Adaptive Immunity

描述（由申请人提供）：Papenfuss博士，D.V.M.，M.S.在临床培训期间，她一直致力于生物医学研究。她完成了MS。在她的D.V.M.培训，已完成了解剖病理学的住院医师培训，是博士候选人。兽医病理生物学，预计毕业日期为2006年春季。Papenfuss博士通过研究激素的免疫调节作用获得了比较病理学，免疫学和疾病免疫发病机制方面的专业知识，因为它们与自身免疫性疾病模型实验性自身免疫性脑脊髓炎（EAE）有关。EAE是多发性硬化症（MS）的动物模型。不仅是理解自身免疫性疾病的重要模型，而且是理解许多疾病的基础免疫机制的有力工具。树突状细胞（DC）是免疫系统的细胞，其驱动炎症并显著影响所得免疫应答的特征。因此，它们是广泛的炎性或免疫介导的病症（例如自身免疫、感染性疾病、过敏和肿瘤学）中的有效治疗靶标。最近的数据鉴定了一种新的经神经调节的树突状细胞群体，其显示出有效的免疫调节能力（即，reg-DC）。总体研究目标是研究激素环境如何产生reg-DCs，这些reg-DCs如何影响炎症和辅助性T细胞发育，并使用动物模型EAE确定这些reg-DCs的治疗潜力。目的1将评估reg-DCs的表型和功能特征，并确定来自激素环境的reg-DCs影响适应性免疫应答和EAE的能力。目的2确定共刺激分子（PD-L1、PD-L2）、可溶性因子（即IL-10、吲哚胺2，3-双加氧酶、IL-12和TNF-α）对reg-DCs如何促进EAE中的保护的相对贡献，目的3将确定雌激素受体在reg-DCs产生中的作用。工作环境：该研究将在实验室内进行，并在申办者Caroline Whitacre博士的指导下进行，Caroline Whitacre博士是基础免疫学，T细胞生物学和EAE的公认专家。这项工作将在分子病毒学、免疫学、医学遗传学和兽医生物科学系内进行。这两个部门的综合资源，与俄亥俄州州立大学的研究人员的合作环境，以及Whitacre博士和OSU同事提供的广泛合作，将为Papenfuss博士在生物医学研究界提供众多合作机会。该SERCA赠款将允许Papenfuss博士投入全职研究培训，促进她发展成为一名独立的科学家，并实现她成为一名学术研究病理学家的终身职业目标。

DESCRIPTION (provided by applicant): Dr. Papenfuss, D.V.M., M.S. has demonstrated continued commitment to biomedical research during her clinical training. She completed an M.S. during her D.V.M. training, has completed a residency in Anatomic Pathology and is a candidate for a Ph.D. in veterinary pathobiology with an expected graduation date of Spring 2006. Dr. Papenfuss has gained expertise in comparative pathology, immunology and the immunopathogenesis of disease by investigating the immunomodulatory effects of hormones as they relate to the autoimmune disease model experimental autoimmune encephalomyelitis (EAE). EAE is an animal model for multiple sclerosis (M.S.) and is an important model for understanding not only autoimmune diseases, but serves as a powerful tool to understand fundamental immunological mechanisms underlying numerous diseases. Dendritic cells (DCs) are cells of the immune system that drive inflammation and dramatically influence the character of the resultant immune response. Thus, they are potent therapeutic targets in a broad range of inflammatory or immune- mediated disorders (e.g. autoimmunity, infectious diseases, allergy and oncology). Recent data identifies a novel population of hormonally modulated dendritic cells demonstrating potent immunoregulatory capabilities (i.e., reg-DCs). The overall research goals are to investigate how hormonal environments can produce reg-DCs, how these reg-DCs influence inflammation and helper T cell development and to determine the therapeutic potential of these reg-DCs using the animal model EAE. Aim 1 will evaluate phenotypic and functional characteristics of reg-DCs and determine the capacity of reg-DCs from hormonal environments to influence the adaptive immune response and EAE. Aim 2 determine the relative contributions of costimulatory molecules (PD-L1, PD-L2), soluble factors (i.e. IL-10, indoleamine 2,3-dioxygenase, IL-12 and TNF-ot) on how reg-DCs promote protection in EAE and Aim 3 will determine the role of estrogen receptors in the generation of reg-DCs. Environment: The research will be performed within the laboratory and under the guidance of the sponsor, Dr. Caroline Whitacre, a recognized expert in fundamental immunology, T cell biology and EAE. The work will be conducted within the Departments of Molecular Virology, Immunology and Medical Genetics and Veterinary Biosciences. The combined resources of these two departments, in conjunction with the collaborative environment of the researchers at the Ohio State University, and the extensive collaborations afforded by Dr. Whitacre and OSU colleagues, will afford Dr. Papenfuss numerous collaborative possibilities within the biomedical research community. The SERCA grant will permit Dr. Papenfuss to devote full time to research training, facilitate her development into an independent scientist and fulfill her lifelong career objectives of becoming an academic research pathologist.