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

胸腺通过提供专门的基质环境来支持T细胞的发育，该环境的功能依赖于单一转录因子FOXN1的存在。已经建立了一种转基因小鼠系，其中小鼠的Foxn1基因被来自文昌鱼的同源基因所取代。在这些小鼠中，T细胞的发育停滞在CD4/CD8双阳性阶段，胸腺和外周仅出现少量的CD4和CD8细胞；胸腺内选择过程看似不完整会导致复杂的自身免疫综合征，主要特征是炎症性肠道疾病和白癜风。利用这个小鼠模型，以及表达鲨鱼Foxn1同源物的第二个品系，缺乏自身免疫功能，本项目旨在通过比较细胞学和分子分析来确定决定胸腺耐受诱导的关键参数。

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.