Regulation of the immune cell glycome in corneal injury

角膜损伤中免疫细胞糖组的调节

• 批准号: 10238839
• 负责人: Pablo Argueso
• 金额: --
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238839
• 关键词: Adaptive Immune System; Address; Adhesions; Affect; Animals; 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; Epithelial; 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 Response; Innate Immune System; Lectin; Leukocyte Trafficking; Leukocytes; Ligands; Light; Mononuclear; Mononuclear Leukocytes; Monosaccharides; Motion; Mus; Organ; Pathologic; Pathway interactions; Play; Polysaccharides; Population; Process; Proteins; Regulation; Research; Role; Selectins; Series; Signal Pathway; Site; Structure; Surface; Tandem Repeat Sequences; Testing; Therapeutic; Tissues; To specify; Vascular Endothelium; adaptive immune response; cell growth; cell motility; cell type; crosslink; gain of function; glycosylation; glycosyltransferase; healing; immune function; immunoregulation; macrophage; monocyte; neutrophil; novel; overexpression; pathogen; prototype; receptor; repaired; sialyl Lewis x; tissue repair; trafficking; translational impact; wound healing

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.

项目总结/摘要 免疫系统由数十亿个不断运动的特化细胞组成， 人体内的稳态。其中，单核细胞是循环单核细胞的群体， 这些细胞可以穿过血管内皮并进入炎症部位，在那里它们参与了炎症反应。 清除病原体和修复受损组织。某些单核细胞表达 细胞外基质的组分将它们定义为纤维细胞。这些细胞群最近 由于它们在各种疾病中对慢性炎症和纤维化的病理贡献， 器官，包括角膜。 对免疫细胞的功能至关重要的是糖萼，一种多样的聚糖混合物， 与环境的主要接口。聚糖在先天免疫和适应性免疫中都起着至关重要的作用， 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簇之一，因为它们促进免疫应答。 与内皮细胞表面表达的细胞粘附分子相互作用。由于其 由于糖组对免疫应答的重要性，过去几年一直需要确定糖组如何影响免疫应答。 免疫细胞的功能受到调节。 越来越清楚的是，半乳糖凝集素作为免疫应答的调节剂发挥关键作用。 它们可以与细胞表面受体相互作用以促进细胞分化，影响细胞生长和存活，并且 调节细胞粘附。我们假设半乳糖凝集素在免疫调节中起着动态作用， 通过引导免疫细胞糖组来进行免疫应答。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单核细胞的糖组，（2）研究半乳糖凝集素的作用， 半乳糖凝集素-3作为活化单核细胞中唾液酸刘易斯X抗原的功能调节剂，以及（3）研究 半乳凝素-3依赖性糖基化在角膜纤维细胞运输和积累中的作用。是 预计这项研究将有重大的翻译影响，鉴于循环纤维细胞的影响， 伤口愈合和疤痕形成。