GC-Tfh cell differentiation

GC-Tfh细胞分化

• 批准号: 10374924
• 负责人: Hui Hu
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-19 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374924
• 关键词: ASCL2 gene; Address; Antibody Response; Autoimmune Diseases; B-Lymphocytes; BLR1 gene; Biological Models; CD4 Positive T Lymphocytes; Candidate Disease Gene; Cell Differentiation process; Cells; Chromatin; Confusion; Data; Dendritic Cells; Genes; Helix-Turn-Helix Motifs; Helper-Inducer T-Lymphocyte; Humoral Immunities; Immune response; In Vitro; Kinetics; Knowledge; Lead; Libraries; Light; Maintenance; Memory; Modeling; Mus; Play; Population; Process; Reporting; Research; Role; Structure of germinal center of lymph node; T memory cell; Work; infectious disease treatment; influenza infection; memory CD4 T lymphocyte; mouse model; multipotent cell; novel; pandemic disease; programmed cell death protein 1; public health relevance; response; transcription factor; transcriptome; vaccine development

Project Summary CD4+ T follicular helper (Tfh) cells are essential for germinal center (GC) responses and long- term humoral immunity. It has been proposed that Tfh cell differentiation is a multi-stage process that includes steps of PD-1+CXCR5+ pre-Tfh and PD-1hiCXCR5hi germinal center Tfh (GC-Tfh) cells. However, most studies have been using the broadly defined “CXCR5+ Tfh” cells, which starts to become too simplistic and may lead to confusion—particularly regarding the GC-Tfh cell differentiation and memory. Dendritic cells activate naïve CD4+ T cells and initiate Tfh cell differentiation including the induction of CXCR5 expression. The further GC-Tfh cell differentiation requires interactions with B cells. Our preliminary results suggest that instead of simple maintenance, pre-Tfh cells undergo substantial further differentiation to become GC-Tfh cells. To a large extent, however, little is known about the mechanism underlying this pre-Tfh to GC-Tfh transition. In this application, we aim to identify novel regulators in pre-Tfh to GC-Tfh cell differentiation. Meanwhile, we will also establish new model systems to study GC-Tfh memory. Our proposal has the potential to provide important knowledge on how to control the humoral immune response for the treatment of infectious diseases, autoimmune disorders, and to aid vaccine development for new pandemic threats.

项目摘要 CD4+ T滤泡辅助器（TFH）细胞对于生发中心（GC）反应至关重要，并且很长 术语的体液免疫。已经提出，TFH细胞分化是一个多阶段的过程 包括PD-1+ CXCR5+ PRE-TFH和PD-1HICXCR5HI生发中心TFH（GC-TFH）细胞的步骤。 但是，大多数研究一直使用广泛定义的“ CXCR5+ TFH”细胞，该细胞开始开始 变得过于简单，可能导致混乱 - 尤其是关于GC-TFH细胞的分化 和内存。 树突状细胞激活幼稚的CD4+ T细胞，并启动TFH细胞分化 CXCR5表达的诱导。进一步的GC-TFH细胞分化需要与B相互作用 细胞。我们的初步结果表明，预先进行TFH细胞而不是简单维护 大大的分化为GC-TFH细胞。但是，在很大程度上很少知道 关于此前TFH到GC-TFH转变的基础机制。在此应用程序中，我们的目标是 鉴定TER-TFH中​​的新型调节剂至GC-TFH细胞分化。同时，我们还将建立新的 研究GC-TFH内存的模型系统。我们的建议有可能提供重要的 有关如何控制治疗传染病的体液免疫反应的知识， 自身免疫性疾病，并帮助疫苗开发新的大流行威胁。