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 CD 4+滤泡辅助性T细胞（Tfh）是生殖中心（GC）反应和长期免疫反应所必需的。 术语体液免疫。已经提出Tfh细胞分化是一个多阶段过程， 包括PD-1+ CXCR 5 + pre-Tfh和PD-1hiCXCR 5 hi生发中心Tfh（GC-Tfh）细胞的步骤。 然而，大多数研究一直使用广义的“CXCR 5 + Tfh”细胞，其开始 变得过于简单，并可能导致混淆-特别是关于GC-Tfh细胞分化 和记忆 树突状细胞激活幼稚CD 4 + T细胞并启动Tfh细胞分化，包括Tfh细胞分化。 诱导CXCR 5表达。GC-Tfh细胞的进一步分化需要与B的相互作用 细胞我们的初步结果表明，前Tfh细胞不是简单的维持， 实质上进一步分化为GC-Tfh细胞。然而，在很大程度上， 关于这种前Tfh到GC-Tfh转变的机制。在本申请中，我们的目标是 鉴定前Tfh至GC-Tfh细胞分化中新调节剂。与此同时，我们还将建立新的 模型系统来研究GC-Tfh记忆。我们的建议有可能提供重要的 关于如何控制体液免疫应答以治疗感染性疾病的知识， 自身免疫性疾病，并帮助疫苗开发新的大流行威胁。