Regulation of the immune cell glycome in corneal injury

角膜损伤中免疫细胞糖组的调节

基本信息

批准号：
10636875
负责人：
Pablo Argueso
金额：
$ 24.72万
依托单位：
TUFTS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10636875
关键词：
Adaptive Immune System Adhesions Affect Animals Binding Biological Process Blood Circulation Blood Group Antigens Bone Marrow CD15 Antigens Cell Adhesion Cell Adhesion Molecules Cell Differentiation process Cell Surface Receptors Cell Survival Cell physiology Cell surface Cells Chimera organism Chronic Cicatrix Cornea Corneal Injury Data Dendritic Cells Endothelial Cells Endothelium Environment Enzymes Epithelium Extracellular Matrix Fibrosis Galactose Binding Lectin Galectin 3 Generations Glycocalyx Glycoconjugates Glycoside Hydrolases Homeostasis Homing Human Human body Immune Immune response Immune system Immunity Immunologic Deficiency Syndromes Immunology Immunomodulators Impairment Inflammation Inflammatory Inflammatory Response Innate Immune Response Innate Immune System Lectin Leukocyte Trafficking Leukocytes Ligands Macrophage Mononuclear Mononuclear Leukocytes Monosaccharides Motion Mus Organ Pathologic Pathway interactions Play Polysaccharides Population Process Protein Glycosylation Proteins Regulation Research Role Selectins Series Signal Pathway Site Specific qualifier value Structure Surface Tandem Repeat Sequences Testing Therapeutic Tissues Vascular Endothelium adaptive immune response cell growth cell motility cell type crosslink gain of function glycosylation glycosyltransferase healing immune function immunoregulation loss of function monocyte neutrophil novel overexpression pathogen prototype receptor repaired sialyl Lewis x tissue repair trafficking translational impact wound healing

项目摘要

Project Summary/Abstract The immune system consists of billions of specialized cells in constant motion that function to maintain homeostasis within the human body. Among them, monocytes are a population of circulating mononuclear cells that can cross the vascular endothelium and move into sites if inflammation, where they participate in the clearance of pathogens and the repairing of damaged tissue. The ability of certain monocytes to express components of the extracellular matrix defines them as fibrocytes. This cell population has recently come under intense scrutiny due to their pathological contribution to chronic inflammation and fibrosis in a variety of organs, including the cornea. Critical to the functions of the immune cells is the glycocalyx, a diverse mixture of glycans that functions as the primary interface with the environment. Glycans play a vital role in both the innate and adaptive immune systems by regulating signaling pathways and the activation of multiple cell types. The Lewis blood group antigens are among the most important cell surface glycan determinants in immunology, as they promote interaction with cell adhesion molecules expressed on the surface of endothelial cells. Because of its significance to the immune reponse, there has been a need for the past few years to define how the glycome of immune cells is regulated. It has become increasingly clear that galectins play a critical role as modulators of the immune response. They can interact with cell surface receptors to promote cell differentiation, affect cell growth and survival, and modulate cell adhesion. We hypothesize that galectins play a dynamic role in the regulation of the immune response by directing the immune cell glycome. The following specific aims will address this objective: (1) to determine whether galectins influence the glycome of human mononuclear cells, (2) to investigate the role of galectin-3 as a functional regulator of the sialyl Lewis X antigen in activated monocytes, and (3) to investigate the role of galectin-3-dependent glycosylation in the trafficking and accumulation of corneal fibrocytes. It is anticipated that this research will have significant translational impact given the impact of circulating fibrocytes to wound healing and scar formation.

项目概要/摘要免疫系统由数十亿个不断运动的专门细胞组成，其功能是维持人体内的稳态。其中，单核细胞是循环单核细胞的群体细胞可以穿过血管内皮并进入炎症部位，在那里它们参与清除病原体和修复受损组织。某些单核细胞的表达能力细胞外基质的成分将它们定义为纤维细胞。这个细胞群最近来了由于它们对多种慢性炎症和纤维化的病理贡献而受到严格审查器官，包括角膜。糖萼对免疫细胞的功能至关重要，它是多种聚糖的混合物，其功能如下：与环境的主要界面。聚糖在先天免疫和适应性免疫中发挥着至关重要的作用通过调节信号通路和多种细胞类型的激活来调节系统。刘易斯血型抗原是免疫学中最重要的细胞表面聚糖决定因素之一，因为它们促进与内皮细胞表面表达的细胞粘附分子相互作用。由于其由于糖组对免疫反应具有重要意义，过去几年一直需要定义糖组如何免疫细胞的数量受到调节。越来越清楚的是，半乳糖凝集素作为免疫反应调节剂发挥着关键作用。它们可以与细胞表面受体相互作用，促进细胞分化，影响细胞生长和存活，并调节细胞粘附。我们假设半乳糖凝集素在免疫调节中发挥动态作用通过指导免疫细胞糖组来做出反应。以下具体目标将实现这一目标：(1) 确定半乳糖凝集素是否影响人类单核细胞的糖组，（2）研究 galectin-3 作为激活单核细胞中唾液酸 Lewis X 抗原的功能调节剂，以及 (3) 研究半乳糖凝集素 3 依赖性糖基化在角膜纤维细胞运输和积累中的作用。这是鉴于循环纤维细胞的影响，预计这项研究将产生重大的转化影响促进伤口愈合和疤痕形成。