Dendritic Cells: Role in Ocular Mucosal Immune Responses

树突状细胞：在眼粘膜免疫反应中的作用

• 批准号: 6733471
• 负责人: Paul C. Montgomery
• 金额: $ 30.2万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6733471
• 关键词: antigen presentation; cellular immunity; dendritic cells; enzyme linked immunosorbent assay; eye; flow cytometry; immunocytochemistry; immunoglobulin A; immunoglobulin G; laboratory rat; lymphatic tissue; mucosal immunity; polymerase chain reaction; tissue /cell culture

DESCRIPTION (provided by applicant): The focus of these studies is to define the role of dendritic cells in ocular-associated mucosal immune responses in order to achieve the long-term objective of developing novel, clinically relevant immunization strategies to protect the external ocular compartment. The hypotheses to be tested are: 1. antigen uptake and delivery to ocular-related lymphoid inductive sites is mediated by dendritic cells and potentiated by factors that activate the dendritic cell maturation program; 2. dendritic cell targeted immunomodulators determine the strength and outcome of ocular mucosal immune responses; and 3. dendritic cells play a role in the effector stage of ocular mucosal immune responses. These hypotheses will be tested by pursuing the following Specific Aims: AIM 1. To define conditions that enhance antigen localization in ocular-related mucosal inductive sites. This aim will phenotypically identify cell types involved in antigen uptake from the ocular or nasal surface and translocation to nasal associated or cervical lymphoid tissues following ocular-topical or intranasal immunization as well as investigate dendritic cell (DC)-targeted strategies to enhance antigen uptake and translocation to lymphoid inductive sites. AIM 2. To determine the role of dendritic cells in the inductive phase of ocular immune responses. This aim will utilize an in vitro system to assay DC maturation and polarization, develop in vivo mucosal immunization protocols to activate DC maturation and polarization programs for enhanced tear IgA and systemic IgG antibody responses and investigate the involvement of plasmacytoid DC in ocular immune responses. AIM 3. To investigate the role of dendritic cells in the effector stage of ocular immune responses. This aim will utilize dendritic cell targeted immunization protocols to investigate the presence of lacrimal gland dendritic cell populations during ocular effector responses, mechanisms facilitating dendritic cell recruitment to lacrimal gland and functions of lacrimal gland dendritic cells. It is expected that a detailed understanding of the role of dendritic cells in the inductive and effector phases of ocular-associated mucosal immune responses will provide information essential to the development of new, clinically relevant vaccination strategies that will optimize protection of the ocular surface.

描述（由申请人提供）：这些研究的重点是定义树突状细胞在眼部相关的粘膜免疫反应中的作用，以实现开发新型的，临床上相关的免疫策略以保护外部眼部隔室的长期目标。要测试的假设是：1。抗原摄取和递送到眼镜相关的淋巴电感部位是由树突状细胞介导的，并通过激活树突状细胞成熟程序的因素增强。 2。树突状细胞靶向免疫调节剂确定眼粘膜免疫反应的强度和结果；和3。树突状细胞在眼部粘膜免疫反应的效应阶段起作用。这些假设将通过追求以下特定目的来检验：目的1。定义可以增强眼部相关粘膜诱导部位抗原定位的条件。该目标将在眼部或鼻腔内或鼻内免疫后的抗原摄取以及迁移到鼻相关或颈淋巴组织中的抗原摄取的细胞类型，并研究树突状细胞（DC）策略，以增强抗抗血液的摄取和转运式脂肪诱导。目标2。确定树突状细胞在眼部免疫反应的电感阶段的作用。该目标将利用体外系统来测定直流成熟和极化，开发体内粘膜免疫协议，以激活DC成熟和极化程序，以增强泪液IgA和全身性IgG抗体反应，并研究血浆乳剂DC在Ocular免疫反应中的参与。目的3。研究树突状细胞在眼部免疫反应效应阶段的作用。该目的将利用树突状细胞靶向免疫方案来研究眼部效应反应期间富集腺树突状细胞群的存在，促进树突状细胞募集到泪腺的机制以及富集腺腺树突状细胞的功能。可以预期，对树突状细胞在眼部相关粘膜免疫反应的感应和效应阶段的作用的详细理解将为开发新的，临床相关的疫苗接种策略提供必不可少的信息，以优化对眼表面的保护。