Molecular basis for the generation of a self-tolerant TCR repertoire (B07*)

产生自耐受 TCR 库的分子基础 (B07*)

• 批准号: 425491371
• 金额: --
• 依托单位: Abteilung Entwicklung des Immunsystems
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/425491371?language=en
• 关键词: Molecular; basis; generation; self; tolerant

The thymus supports T-cell development through the provision of a dedicated stromal environment, whose function depends on the presence of a single transcription factor, FOXN1. A transgenic mouse line has been developed, in which the mouse Foxn1 gene is replaced by its homologue from the cephalochordate amphioxus. In these mice, T-cell development stalls at the CD4/CD8 double-positive stage, with only few CD4 and CD8 cells appearing in the thymus and the periphery; the seemingly incomplete intrathymic selection processes cause a complex autoimmune syndrome, chiefly characterized by inflammatory bowel disease and vitiligo. Using this mouse model, and a second line expressing Foxn1 homologues from sharks, which lacks autoimmune features, this project aims at identifying the key parameters determining thymic tolerance induction by comparative cytological and molecular analyses.

胸腺通过提供专用的基质环境来支持T细胞发育，其功能取决于单个转录因子FOXN 1的存在。已经开发了转基因小鼠品系，其中小鼠Foxn 1基因被其来自头索动物文昌鱼的同源物取代。在这些小鼠中，T细胞发育停滞在CD 4/CD 8双阳性阶段，只有少数CD 4和CD 8细胞出现在胸腺和外周;看似不完整的胸腺内选择过程导致复杂的自身免疫综合征，主要特征是炎症性肠病和白癜风。使用这种小鼠模型，和第二行表达Foxn 1同源鲨鱼，缺乏自身免疫功能，该项目的目的是通过比较细胞学和分子分析确定确定胸腺耐受诱导的关键参数。