Galectin-1's effects on dendritic cell function.

Galectin-1 对树突状细胞功能的影响。

• 批准号: 7676449
• 负责人: Margaret Chang
• 金额: $ 2.97万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 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/7676449
• 关键词: Affect; Antigen-Presenting Cells; Autoimmune Diseases; Autoimmunity; Binding; Biochemical; Bioinformatics; Biological; Biology; Cell Differentiation process; Cell Maturation; Cell physiology; Cells; Characteristics; Complement component C1s; 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; Interleukin-1 Receptors; Knockout Mice; Laboratories; Lead; Lectin; Mediating; Mediator of activation protein; Mentors; 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; Training; Viral; 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

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”最适当反应的显著能力。它们在促进先天性和适应性免疫中具有已知的作用，并且越来越多的证据支持它们在稳态条件下在免疫耐受中的作用。虽然DC对外源性刺激的反应已得到很好的研究，但对激活和调节DC的内源性信号知之甚少。半乳糖凝集素-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。半乳糖凝集素-1也可以对相同的细胞具有不同的作用，这取决于凝集素的浓度和细胞的活化状态。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独特地激活人单核细胞衍生的DC成熟，同时增强其通过细胞外基质的迁移。由于DC是由处于不同分化和活化阶段的功能不同的亚群组成的动态群体，因此我认为半乳糖凝集素-1在DC分化和成熟的不同阶段具有不同的作用。半乳糖凝集素-1对DC的免疫调节功能将在以下具体目标中表征：目标1：鉴定半乳糖凝集素-1诱导成熟的信号介质。我将使用生物抑制剂和基因敲除小鼠模型来鉴定半乳糖凝集素-1所利用的关键信号分子和受体。目的2：探讨galectin-1对不同分化成熟阶段DC的免疫调节作用。我将使用体外和体内模型来评估半乳糖凝集素-1处理的DC调节免疫应答的能力。最终，这些关于半乳糖凝集素-1对DCs免疫调节功能的作用和机制的研究将导致免疫疾病的新治疗方法。半乳糖凝集素-1对改善自身免疫性疾病具有良好的作用。这些研究将确定半乳糖凝集素-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。基于免疫的疾病具有毁灭性的影响，治疗具有挑战性，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性疫苗已经取得了一些成功。对树突状细胞的生物学及其在免疫发病机制中的作用的更好理解将形成用于基于免疫的疾病的新型靶向疗法的理论基础。