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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.

项目总结/文摘