Cellular and Genetic Analysis of Lymphocyte Egress

淋巴细胞排出的细胞和遗传分析

• 批准号: 9066060
• 负责人: Jason G Cyster
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9066060
• 关键词: Address; Antigens; Autoimmune Diseases; Award; B-Lymphocytes; Blood; Blood Circulation; Blood-Borne Pathogens; Cells; Clinical; Data; Dendritic Cells; Development; Effector Cell; Epithelium; Goals; Grant; Immune; Immune System Diseases; Immune response; Immunologic Surveillance; Immunosuppressive Agents; Infection; Inflammatory; Knowledge; Ligands; Lymph; Lymphatic; Lymphatic Endothelium; Lymphatic vessel; Lymphocyte; Lymphoid; Lymphoid Tissue; Malpighian corpuscles; Microscopy; Modeling; Molecular; Movement; Oral; Organ; Pathway interactions; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Procedures; Role; Site; Skin; Source; Sphingosine-1-Phosphate Receptor; Spleen; Splenic Red Pulp; Structure of aggregated lymphoid follicle of small intestine; Structure of germinal center of lymph node; T-Lymphocyte; Testing; Thymus Gland; Time; Tissue Model; Tissues; Travel; Work; cell motility; cell type; follow-up; genetic analysis; immune function; intravital microscopy; lymph nodes; migration; multiple sclerosis treatment; novel therapeutics; response; sphingosine 1-phosphate; targeted treatment; therapeutic development; tool; trafficking; two-photon

DESCRIPTION (provided by applicant): The molecular mechanism of cell entry from blood into tissues has been intensely studied over more than three decades. This work has led to a well-defined multistep model of tissue entry by cells and the development of approved therapeutic agents that target entry as a treatment for immunological diseases. Cell egress from tissues into circulation is equally important for immune function yet has been a focus of study for only the last several years. The potential clinical impact of developing agents to modulate cell egress has been highlighted by the September 2010 approval of FTY720 (Fingolimod), a drug that inhibits lymphocyte egress from lymphoid organs, as the first oral treatment for multiple sclerosis. FTY720 is a ligand for four of five sphingosine-1-phosphate (S1P) receptors. T and B cell egress from lymph nodes, spleen and Peyer's patches is dependent on S1P and S1P receptor-1 (S1PR1). This proposal will identify the pathway of B cell egress from the spleen into blood. Secondly, it will characterize how S1PR1 regulates marginal zone B cell movement and antigen transport between subcompartments within the spleen. Thirdly, it will explore the role of a migration- inhibitory S1P receptor, S1PR2, in controlling egress of cells from non-lymphoid tissues into lymph. This work will elucidate key requirements for lymphocyte egress from lymphoid and non-lymphoid tissues, findings that may help in the development of new therapeutics for treatment of autoimmune diseases.

描述（由申请人提供）：细胞从血液进入组织的分子机制已经被深入研究了三十多年。这项工作导致了细胞进入组织的一个明确的多步骤模型，并开发了经批准的靶向进入的治疗药物，作为免疫疾病的治疗方法。细胞从组织进入循环对免疫功能同样重要，但一直是研究的焦点

项目成果

The C2H2-ZF transcription factor Zfp335 recognizes two consensus motifs using separate zinc finger arrays.

• DOI: 10.1101/gad.279406.116
• 发表时间: 2016-07-01
• 期刊: Genes & development
• 影响因子: 10.5
• 作者: Han BY;Foo CS;Wu S;Cyster JG
• 通讯作者: Cyster JG

Neural crest-derived pericytes promote egress of mature thymocytes at the corticomedullary junction.

• DOI: 10.1126/science.1188222
• 发表时间: 2010-05-28
• 期刊: Science (New York, N.Y.)
• 作者: Zachariah MA;Cyster JG
• 通讯作者: Cyster JG

CD69 suppresses sphingosine 1-phosophate receptor-1 (S1P1) function through interaction with membrane helix 4.

• DOI: 10.1074/jbc.m110.123299
• 发表时间: 2010-07-16
• 期刊: The Journal of biological chemistry
• 作者: Bankovich AJ;Shiow LR;Cyster JG
• 通讯作者: Cyster JG

GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood.

• DOI: 10.1126/science.1208248
• 发表时间: 2011-09-30
• 期刊: Science (New York, N.Y.)
• 作者: Arnon TI;Xu Y;Lo C;Pham T;An J;Coughlin S;Dorn GW;Cyster JG
• 通讯作者: Cyster JG