Retinoid Nutritional Status and Immune Function

类维生素A营养状况和免疫功能

基本信息

批准号：
8013381
负责人：
A. CATHARINE ROSS
金额：
$ 9.41万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-19 至 2012-02-18
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8013381
关键词：
Adult Affect All-Trans-Retinol Animal Model Anti-Infective Agents Antibodies Antibody Formation Antibody-Producing Cells Antigen-Presenting Cells Antigens B-Cell Activation B-Lymphocytes Biochemical CD38 molecule CD4 Positive T Lymphocytes Cell Differentiation process Cell Maturation Cell physiology Cell surface Cells Child Communicable Diseases Competence Confocal Microscopy Dendritic Cells Disease Down-Regulation Equilibrium Family member Flow Cytometry Glycolipids Goals Grant Helper-Inducer T-Lymphocyte Humoral Immunities Immune Immune response Immune system Immunity Immunization Immunoassay Immunocompromised Host Individual Infant Interleukin-4 Life Ligands Lymphocyte Activation Measles Memory Microscopic Modeling Molecular Analysis Morbidity - disease rate Mucosal Immunity Mus Neonatal Nutritional Nutritional status Outcome Plasma Plasma Cells Play Poly I-C Pregnant Women Prevention Production RNA Editing Reaction Regulation Research Research Personnel Retinoids Role Signal Transduction Spleen Staging Stimulus Structure of germinal center of lymph node T-Lymphocyte TLR3 gene Techniques Testing Tetanus Toxoid Thymus Gland Time Toll-like receptors Tretinoin Tumor Necrosis Factor-alpha Tumor Necrosis Factors Up-Regulation Vaccination Vitamin A Vitamin A Deficiency Vitamins Work activation-induced cytidine deaminase adaptive immunity aged base clinically relevant cytokine human TLR3 protein immune function in vivo killer T cell mortality named group neonate programs receptor transcription factor

项目摘要

DESCRIPTION (provided by applicant): Vitamin A and its active metabolite, retinoic acid (RA), affect the immune system in multiple ways. Our research is focused on the ability of retinoids to work together with co-stimulatory molecules, of both endogenous and exogenous origin, to promote strong and long-lasting immunity in adults and neonates. Using mice, we have recently shown that a nutritional-immunological combination of RA and a cytokine inducer, poly-l:C (PIC), can act together to stimulate much stronger primary and memory antibody responses in both adult and neonatal mice. Our long-term goal is to understand how RA and co-stimuli can augment antigen-specific antibody responses, especially in the very young and in individuals whose immune system is weakened by vitamin A deficiency or disease. The central hypothesis of this proposal is "Retinoic acid, an active metabolite of VA, cooperates with immunological co-stimuli - especially the Toll-like Receptor (TLR)-3 ligand, poly-l:C (PIC), the signaling co-receptor CD38, and tumor necrosis factor family members - to significantly regulate antibody production at both the neonatal and adult stages of life." We will use a combination of cell and molecular analysis, flow cytometry, confocal microscopy, and immunoassays to better understand how RA and co-stimuli promote the activation of B-cells and the antibody response to immunization in vivo. Our 3 aims are: 1) To determine how RA and costimulatory molecules activate B cells isolated from adult and neonatal mice; 2) To establish how RA and co-stimulation regulate the formation of germinal centers (GC), a specialized microenvironment where antibody-producing cells mature; 3) To test whether a special population of T-cells, referred to as iNKT cells, are responsive to RA plus costimuli, and whether a combined nutritional-immunological treatment can balance the production of cytokines that are needed for an optimal immune response. Relevance: Vaccination is a life-saving strategy for infants and children. Vitamin A's active metabolite, retinoic acid, together with immune stimuli of endogenous and exogenous origin, may be an effective combination for promoting B-lymphocyte activation and the production of a strong, durable antibody response in vivo, as is necessary for protection against infectious disease. Our studies will use biochemical and microscopic techniques to test whether nutritional-immunological combinations of RA plus several immune stimuli, given with immunization, can promote B-cell activation, induce microarchitectural changes needed for strong antibody production, and increase the plasma antibody levels in adult and neonatal mice.

描述（由申请人提供）：维生素A及其活性代谢产酸（RA）以多种方式影响免疫系统。我们的研究集中在类视黄素与内源性和外源性的共同刺激分子一起工作的能力，以促进成人和新生儿的强大和持久的免疫力。使用小鼠，我们最近表明，RA和细胞因子诱导剂Poly-L：C（PIC）的营养免疫组合可以一起起作用，可以刺激成年和新生儿小鼠中更强的原发性和记忆抗体反应。我们的长期目标是了解RA和联合刺激如何增加抗原特异性抗体反应，尤其是在年轻的人和免疫系统因维生素A缺乏症或疾病而削弱的个体中。 The central hypothesis of this proposal is "Retinoic acid, an active metabolite of VA, cooperates with immunological co-stimuli - especially the Toll-like Receptor (TLR)-3 ligand, poly-l:C (PIC), the signaling co-receptor CD38, and tumor necrosis factor family members - to significantly regulate antibody production at both the neonatal and adult stages of life."我们将使用细胞和分子分析，流式细胞仪，共聚焦显微镜和免疫测定的组合，以更好地了解RA和共刺激如何促进B细胞的激活以及对体内免疫的抗体反应。我们的3个目的是：1）确定RA和共刺激分子如何激活从成年和新生小鼠分离的B细胞； 2）建立RA和共刺激如何调节生发中心（GC）的形成，这是一种专门的微环境，其中产生抗体的细胞成熟； 3）测试特殊的T细胞（称为Inkt细胞）是否对RA Plus Costimuli有反应，以及合并的营养 - 免疫学治疗是否可以平衡最佳免疫反应所需的细胞因子的产生。相关性：疫苗接种是婴儿和儿童的救生策略。维生素A的活性代谢产物维生酸，以及内源性和外源性起源的免疫刺激，可能是促进B-淋巴细胞激活和体内强，耐用抗体反应的有效组合，这是保护免受感染疾病所必需的。我们的研究将使用生化和显微镜技术来测试RA的营养 - 免疫性组合以及通过免疫给予的几种免疫刺激是否可以促进B细胞激活，可以促进B细胞激活，诱导强抗体产生所需的微实施变化，并增加成年和新生儿小鼠的血浆抗体水平。