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Transcriptional Regulation of Innate T cell fate

先天 T 细胞命运的转录调控

基本信息

批准号：
10283893
负责人：
Laurent Gapin
金额：
$ 23.33万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-14 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10283893
关键词：
Adaptive Immune System Allergic Animal Model Antigen-Presenting Cells Antigens Autoimmunity Bacteria Bee Venoms CD1 Antigens CD3 Antigens Cell Lineage Cells Chromatin Collection Cytotoxic T-Lymphocytes Data Development Disease Epigenetic Process Event Exposure to Family Family member Genetic Transcription Glycolipids Health Human Immune Immune response Immunity In Vitro Inflammatory Instruction Joints Knowledge Lead Link Mediating Molecular Mucous Membrane Mus Mycobacterium tuberculosis Natural Immunity Output Peripheral Population Process RNA Receptor Activation Receptor Signaling Resolution Rhus radicans Role SLAM protein Shapes Signal Transduction Snake Venoms Specificity System T-Cell Development T-Cell Receptor T-Lymphocyte Testing Therapeutic Intervention Therapeutic Uses Thymus Gland Tissues Transcriptional Regulation Virus Vitamins ZNF145 gene adaptive immunity consumer product cytokine epigenetic regulation epigenome human disease immunoregulation improved neonatal human novel novel therapeutic intervention pathogen exposure precursor cell programs receptor receptor function residence response therapeutic candidate thymocyte transcription factor transcriptome tumor

项目摘要

Project Summary InnateT cells are a collection of T cells withimportant regulatory functions that have a crucial role in immunity towards tumors, bacteria, viruses, and in cell-mediated autoimmunity. Due large quantities of cytokines upon activation, immune response populations glycolipid cells T commitment to innate T cells act as bridges between the innate and adaptive systems a nd ontribute greatly In mice, this swiftness of reflects their acquisition f functionality during their development in the thymus. Three major within the innate T cell group are recognized namely, the invariant NKT cells that recognize antigens presented by non-polymorphic CD1d molecules, the mucosal associated invariant T (MAIT) that recognize vitamin metabolites presented by the non-polymorphic MR1 molecules, and the certain  cells which antigen specificities remain uncertain. We have established an in vitro system t hat mimics the of double positive precursor cells to the innate T cell lineage and we propose to their ability to promptly secrete c to immune regulation and host protection. o , deconstruct the early transcriptional and epigenetic events that accompany this fate commitment (Aim 1). In this way, we will identify manipulation early factors that influence innate T cell development, providing the possibility for selective of innate T cell lineage specification. We will then investigatewhether human innate T cells acquire an innate-like transcriptional program in the thymus similarly to their mouse counterparts and whether this program is shared between the two species. To do so, we will profile the transcriptomes of iNKT and MAIT cells purified from neonatal human thymi at the single cell level. In addition, we will extend our knowledge of innate T cell lineage commitment by also studying CD1a-restricted T cells, which do not exist in mice (Aim 2). Given their capacity to link key inflammatory axes of innate and adaptive immunity, a better understanding of the molecular basis underpinning innate T cell development and plasticity, and how much this feature accounts for their pathophysiological roles, is critical for developing novel therapeutic approaches.

项目总结