Regulation of memory T cell trafficking by core 2 O-glycan synthesis

通过核心 2 O-聚糖合成调节记忆 T 细胞运输

• 批准号: 10242550
• 负责人: Jeffrey C. Nolz
• 金额: $ 7.52万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-18 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242550
• 关键词: Acute; Age; Allergens; Anabolism; Antigens; Area; Autoantigens; Autoimmune Diseases; Autoimmunity; Basic Science; Blood Circulation; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cells; Chronic; Complex; Disease; E-Selectin; Endothelium; Environment; Exhibits; Extravasation; Gene Expression Profiling; Generations; Genes; Genetic Transcription; Glycobiology; Goals; Home environment; Hypersensitivity; Immune; Immunity; Immunotherapy; In Vitro; Infection; Inflammation; Inflammatory; Integrins; Interleukin-15; Life; Ligands; Link; Lymphocyte Homing Receptors; Mediating; Membrane Proteins; Memory; Modeling; Molecular; P-Selectin; Pathogenicity; Pathologic; Pathway interactions; Polysaccharides; Population; Population Heterogeneity; Prevention; Process; Protocols documentation; Regulation; Research; Route; Selectins; Skin; Stat5 protein; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Techniques; Testing; Tissues; Vaccine Design; Vaccines; Vascular Endothelium; Virus Diseases; antiviral immunity; base; chemokine receptor; cytokine; experience; glycosylation; human disease; immunopathology; improved; in vivo; innovation; lymph nodes; memory CD4 T lymphocyte; pathogen; receptor; response; trafficking; transcription factor; vaccine immunotherapy

PROJECT SUMMARY/ABSTRACT Antigen-experienced memory T cells constitute a diverse, heterogeneous population of immune cells that is generated throughout life in response to a variety of pathogens, vaccines, allergens, self-antigens and other environment factors. In fact, as we age, generation of new naïve T cells diminishes and memory T cell populations dominate the repertoire. Thus, the basic mechanisms that regulate the functions of diverse memory T cell populations has broad relevance for a variety of diseases and pathological conditions including vaccine designs, immunotherapy protocols and treatment or prevention of inflammatory or autoimmune disorders. Although the formation and differentiation of memory CD8+ and CD4+ T cells in the circulation has been extensively characterized, the capacity for memory T cells to actively home to and infiltrate tissues where they exhibit their effector functions is less understood. We have recently discovered that memory CD8+ T cells require post-translational O-linked glycosylation of selectin ligands for trafficking to and infiltrating non- lymphoid tissues. Furthermore, we identified that de novo synthesis of core 2 O-glycans is restricted to memory T cells and can be regulated in an antigen-independent manner. However, the basic molecular mechanisms regulating core 2 O-glycan synthesis and trafficking of memory CD8+ and CD4+ T cells during infections are yet to be fully characterized. Specifically, we will 1) determine if different CD8+ T cell populations have the capacity to synthesize core 2 O-glycans and traffic into non-lymphoid tissues, 2) define the molecular and transcriptional mechanisms that regulate core 2 O-glycan synthesis in memory CD8+ T cells, and 3) determine if memory CD4+ T cells require core 2 O-glycan synthesis to traffic into non-lymphoid tissues during either acute or chronic viral infections. Thus, the overall goal of our study will be to identify and characterize the mechanisms regulating the trafficking of diverse memory T cell populations and how this can be enhanced (for host protection) or inhibited (for allergies or autoimmunity).

项目总结/文摘