Control of Lymphocyte Homeostasis by Foxo Transcription Factors

Foxo 转录因子对淋巴细胞稳态的控制

• 批准号: 7529891
• 负责人: STEPHEN M HEDRICK
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7529891
• 关键词: Affect; Antigens; Autoimmune Diseases; Bone Marrow; Boxing; CD80 gene; Cell Size; Cell Survival; Cell physiology; Cells; Cessation of life; Cues; Defect; Dendritic Cells; Exhibits; Family; Fluorescence Microscopy; Funding; Gene Chips; Gene Expression; Genes; Goals; Growth Factor; Hematopoietic; Homeostasis; Homing; Immune; Immune response; Individual; Infection; Inflammatory; Interleukin-6; L-Selectin; Lymphocyte; Lymphoid; Lymphopenia; Maps; Mediating; Mus; Mutation; Nuclear; Nutrient; Organ; Phenotype; Principal Investigator; Publishing; Regulation; Regulatory Pathway; Reporting; Research; Role; Self Tolerance; Signal Pathway; Signal Transduction; Stress; System; T-Cell Activation; T-Lymphocyte; Testing; Transgenic Mice; Viral Antigens; Virus; abstracting; cytokine; design; member; programs; reconstitution; research study; response; tool; transcription factor

Principal Investigator/Program Director (Last, first, middle): Hedrick, Stephen M. 1 R01 AI073885-01A2 PROJECT SUMMARY/ABSTRACT Hematopoietic cells constantly turn over. Their rates of division and death determine the steady-state number of cells and size of lymphoid organs. In particular, T lymphocytes are held in a state of active quiescence that can be relieved to allow for dramatic expansions and contractions associated with infection. Whether there is a connection between active quiescence, homeostasis, regulation of antigen-mediated expansion and tolerance is presently lmknown. The hypothesis to be tested in this proposal is that some or all of these aspects of T cell physiology are importantly regulated by a family of transcription factors known to integrate multiple inputs: growth factors, nutrients, and stress. This family has been termed FOXO for Forkhead bOX with the second 0 denoting one of 19 subfamilies consisting of five members related by sequence. We find that Foxo1 and Foxo3 mediate important regulatory functions in T cells and dendritic cells, respectively. The experiments described in this application are designed to lmderstand the mechanisms lmderlying this regulation, and determine how Foxo factors regulate lymphoproliferation, survival, autoimmune disease, and self-tolerance.

首席研究员/计划总监（最后，第一，中间）：Hedrick，Stephen M. 1 R01 AI073885-01A2 项目摘要/摘要 造血细胞不断转移。他们的分裂和死亡率决定了细胞的稳态数量和淋巴器官的大小。特别是，T淋巴细胞保持在活跃的静止状态，可以放心，以允许与感染相关的显着膨胀和收缩。目前已知是否存在主动静止，体内平衡，抗原介导的膨胀和耐受性之间的联系。该提议中要检验的假设是，T细胞生理学的某些或所有这些方面都由已知整合多个输入的转录因子家族来调节：生长因子，养分和压力。这个家庭被称为foxo for forkhead盒子，第二个0表示19个亚家族之一，由五个按顺序相关的成员组成。我们发现FOXO1和FOXO3分别介导了T细胞和树突状细胞中的重要调节功能。本应用中描述的实验旨在遵循该调节的机制，并确定FOXO因素如何调节淋巴增生，生存，自身免疫性疾病和自我耐受性。