Galectin-1's effects on dendritic cell function.

Galectin-1 对树突状细胞功能的影响。

基本信息

批准号：
8127678
负责人：
Margaret Chang
金额：
$ 3.57万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8127678
关键词：
Affect Antigen-Presenting Cells Autoimmune Diseases Autoimmunity Binding Biochemical Bioinformatics Biological Biology Cell Differentiation process Cell Maturation Cell physiology Cells Characteristics Complex Dendritic Cells Disease Environment Extracellular Matrix Family Galactose Binding Lectin Galactosides Galectin 1 Genetic Programming Glycobiology Human Immune Immune Tolerance Immune response Immunity Immunologist Immunotherapy In Vitro Inflammation Inflammatory Interleukin-1 Knockout Mice Laboratories Lead Lectin Mediating Mediator of activation protein Mentors Natural Immunity Neoplasm Metastasis Pathogenesis Patients Phenotype Population Dynamics Production Property Publications Recording of previous events Regulation Role Signal Transduction Signaling Molecule Staging Stimulus Symptoms T-Lymphocyte TNF gene Training Viral adaptive immunity base body system cell growth cell motility cytokine improved in vivo in vivo Model inhibitor/antagonist insight migration monocyte mouse model novel novel therapeutic intervention pathogen receptor receptor expression response skills success therapeutic vaccine

项目摘要

DESCRIPTION (provided bny applicant): Dendritic cells (DCs) have a remarkable ability to interpret environmental information and then "decide" the most appropriate response. They have known roles in promoting innate and adaptive immunity, and accumulating evidence supports their role in immune tolerance during steady state conditions. While DC responses to exogenous stimuli are well studied, less is known about endogenous signals that activate and regulate DCs. Galectin-1 is an endogenous galactoside-binding lectin that has a broad range of immunomodulatory abilities on various innate and adaptive immune cells. Galectin-1 can also have different effects on the same cell depending on the concentration of the lectin and the activation state of the cell. Notably, our laboratory recently made a novel observation that galectin-1 uniquely activates human monocyte-derived DCs to mature while enhancing their migration through extracellular matrix. Because DCs are a dynamic population consisting of functionally distinct subsets in varying stages of differentiation and activation, I posit that galectin-1 will have different effects at various stages of DC differentiation and maturation. The immunomodulatory function of galectin-1 on DCs will be characterized in the following specific aims: Aim 1: To identify the signaling mediators of galectin-1 induced maturation. I will use biological inhibitors and knock-out mouse models to identify the key signaling molecules and receptors utilized by galectin-1. Aim 2: To determine the immunomodulatory functions of galectin-1 on DCs at different stages of differentiation and maturation. I will use in vitro and in vivo models to assess the ability of galectin-1 treated DCs to regulate immune responses. Ultimately, these studies on the role and mechanism of galectin-1 on the immunomodulatory functions of DCs will lead to novel therapeutic approaches to immune-based diseases. Galectin-1 has well-documented effects on ameliorating autoimmune diseases. These studies will establish whether regulation of DC function by galectin-1 contributes to the promotion of immune tolerance and avoidance of autoimmunity. Immune-based diseases are devastating in their effects and challenging to treat, with complex symptoms involving major and multiple organ systems. Recently, there has been some success with patient-specific therapeutic vaccines based upon dendritic cells. Improved understanding of the biology of dendritic cells and their roles in immune pathogenesis will form the rationale for novel targeted therapies for immune-based diseases.

描述（由申请人提供）：树突状细胞（DC）具有解释环境信息并随后“决定”最合适反应的非凡能力。它们在促进先天性和适应性免疫方面发挥着已知的作用，并且越来越多的证据支持它们在稳定状态条件下的免疫耐受中的作用。虽然 DC 对外源刺激的反应已得到充分研究，但对激活和调节 DC 的内源信号知之甚少。 Galectin-1 是一种内源性半乳糖苷结合凝集素，对各种先天性和适应性免疫细胞具有广泛的免疫调节能力。根据凝集素的浓度和细胞的激活状态，Galectin-1 还可对同一细胞产生不同的作用。值得注意的是，我们的实验室最近进行了一项新的观察，即半乳糖凝集素-1 独特地激活人类单核细胞来源的 DC 成熟，同时增强其通过细胞外基质的迁移。由于 DC 是一个动态群体，由处于不同分化和激活阶段的功能不同的子集组成，因此我认为 galectin-1 在 DC 分化和成熟的不同阶段会产生不同的影响。 galectin-1 对 DC 的免疫调节功能将在以下具体目标中进行表征：目标 1：鉴定 galectin-1 诱导成熟的信号传导介质。我将使用生物抑制剂和基因敲除小鼠模型来识别 galectin-1 使用的关键信号分子和受体。目的2：确定galectin-1对分化和成熟不同阶段的DC的免疫调节功能。我将使用体外和体内模型来评估 galectin-1 处理的 DC 调节免疫反应的能力。最终，这些关于 galectin-1 对 DC 免疫调节功能的作用和机制的研究将为基于免疫的疾病带来新的治疗方法。 Galectin-1 在改善自身免疫性疾病方面具有良好的作用。这些研究将确定galectin-1对DC功能的调节是否有助于促进免疫耐受和避免自身免疫。免疫性疾病具有毁灭性的影响，并且治疗起来具有挑战性，其症状复杂，涉及主要和多个器官系统。最近，基于树突状细胞的患者特异性治疗疫苗取得了一些成功。加深对树突状细胞生物学及其在免疫发病机制中的作用的了解，将为免疫疾病的新型靶向治疗奠定基础。