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Transcriptional regulation of T cell quiescience and activation

T 细胞静止和激活的转录调控

基本信息

批准号：
8872018
负责人：
Hui Hu
金额：
$ 36.75万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8872018
关键词：
Acute Affect Aging Agonist Antigens Autoimmune Diseases B-Lymphocytes Binding Sites Biological Models Boxing Cell Cycle Cell Lineage Cell Survival Cells Communicable Diseases Data Development Effector Cell Enhancers Family Feedback Gene Targeting Goals Homeostasis Immune response Interleukin-7 Knowledge Length MEKs Malignant Neoplasms Mature T-Lymphocyte Mediating Memory Metabolism Modeling Molecular Molecular Target Mus Pathway interactions Peripheral Phase Phenotype Play Proliferating Protein Isoforms Proteins Receptor Signaling Regulation Regulator Genes Research Role Signal Transduction T Cell Receptor Signaling Pathway T cell regulation T memory cell T-Cell Activation T-Cell Receptor T-Lymphocyte Thymocyte Development Tissues Transcriptional Regulation Transgenes Transgenic Mice Variant Virus Diseases chromatin modification design forkhead protein in vivo insight member mouse model novel novel therapeutics response thymocyte transcription factor vaccine development

项目摘要

DESCRIPTION (provided by applicant): The quiescent state of peripheral naive T lymphocytes was thought to be due to the lack of activation signals. Recent studies, however, have shown that T cell quiescence is not by default but actively maintained by both cell extrinsic and intrinsic mechanisms, about which little is known at the transcriptional level. Forkhead box (FOX) proteins comprise a large family of transcription factors with diverse functions in development, aging and cancer. Recently we discovered that transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells, providing direct evidence that mature T cell quiescence is actively maintained. Meanwhile, our new preliminary studies also start to reveal that Foxp1 transcriptional network plays an important role in agonist- induced T cell activation. In this proposal, we will combine various approaches to identify functional targets and molecular pathways regulated by Foxp1 in controlling T cell quiescence, and to define the critical roles of Foxp1 in antigen-induced T cell activation and responses in vivo. Knowledge obtained from these studies will provide information for the design of new therapeutic strategies that would manipulate T cell activation status for the treatment of autoimmune and infectious diseases, and aid in vaccine development.

描述(申请人提供)：外周幼稚T淋巴细胞的静止状态被认为是由于缺乏激活信号所致。然而，最近的研究表明，T细胞的静止不是默认的，而是由细胞外在和内在机制积极维持的，而在转录水平上对此知之甚少。Forkhead box(Fox)蛋白是一个转录因子大家族，在发育、衰老和癌症中具有不同的功能。最近我们发现转录因子Foxp1对幼稚T细胞的静止起着重要的细胞内源性调节作用，这为成熟T细胞的静止被积极地维持提供了直接证据。同时，我们新的初步研究也开始揭示foxp1转录网络在激动剂诱导中起重要作用。 T细胞活化。在这个方案中，我们将结合不同的方法来确定Foxp1调控T细胞静止的功能靶点和分子途径，并确定Foxp1在体内抗原诱导的T细胞激活和反应中的关键作用。从这些研究中获得的知识将为设计新的治疗策略提供信息，这些策略将操纵T细胞的激活状态来治疗自身免疫和传染病，并有助于疫苗的开发。