Hormonal Modulation of DCs: Influences on Innate and Adaptive Immunity

描述(申请人提供)：Papenfuss博士，D.V.M.，M.S.在她的临床培训期间表现出对生物医学研究的持续承诺。她在接受D.V.M.培训期间完成了硕士学位，完成了解剖病理学的住院医师资格，是兽医病理生物学博士候选人，预计毕业日期为2006年春季。Papenfuss博士通过研究激素与自身免疫性疾病模型实验性自身免疫性脑脊髓炎(EAE)相关的免疫调节作用，在比较病理学、免疫学和疾病的免疫发病机制方面获得了专业知识。EAE是多发性硬化症(MS)的动物模型。它不仅是了解自身免疫性疾病的重要模型，而且是了解多种疾病的基本免疫学机制的有力工具。树突状细胞(DC)是免疫系统中的细胞，它驱动炎症并极大地影响所产生的免疫反应的特征。因此，它们是广泛的炎症性或免疫介导性疾病(如自身免疫、传染病、过敏和肿瘤学)的有效治疗靶点。最近的数据表明，一种新的激素调节的树突状细胞群体显示出强大的免疫调节能力(即，REG-DC)。总的研究目标是研究激素环境如何产生REG-DC，这些REG-DC如何影响炎症和辅助T细胞的发展，并使用动物模型EAE来确定这些REG-DC的治疗潜力。目的1评估REG-DC的表型和功能特征，确定激素环境中的REG-DC影响获得性免疫反应和EAE的能力。目的2确定共刺激分子(PD-L1、PD-L2)、可溶性因子(IL-10、吲哚胺2，3-双加氧酶、IL-12和肿瘤坏死因子-ot)在EAE中促进保护作用的相对作用，目的3确定雌激素受体在REG-DC生成中的作用。环境：研究将在实验室内进行，并在赞助商Caroline Whituck博士的指导下进行，她是基础免疫学、T细胞生物学和EAE方面的公认专家。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。这两个部门的资源结合在一起，再加上俄亥俄州立大学研究人员的协作环境，以及惠塔克博士和俄亥俄州立大学同事提供的广泛合作，将为帕彭法斯博士在生物医学研究领域提供无数的合作可能性。SERCA的拨款将允许Papenfuss博士将全部时间投入研究培训，促进她发展成为一名独立科学家，并实现她成为一名学术研究病理学家的毕生职业目标。

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.