Molecular Regulation of Aging Thymus Atrophy

描述（申请人提供）：免疫衰老始于胸腺复旧，而年龄相关性胸腺复旧是由多基因调控的胸腺微环境变化引起的。我们的假设是衰老萎缩的胸腺一定表现出目前尚不清楚的分子特征和细胞谱的变化，主要由胸腺上皮细胞构建的调节胸腺微环境的转录因子可能参与了衰老相关的胸腺退化过程。我们的方法是研究衰老萎缩胸腺的分子特征和细胞谱，重点关注K5/K8在胸腺上皮细胞、TN.1造血祖细胞亚群上的共定位，基于cKit和HAS的表达，以及两类Foxnl转录的表达；同时，通过部位和时间组织特异性的crer -recombinase小鼠模型，检测下调成年胸腺髓质、皮质和总TECs中的Foxn1信号是否能充分诱导衰老相关的胸腺复旧。这些研究可能最终导致理解与年龄相关的胸腺退化的分子机制，并使逆转老年胸腺功能的策略成为可能。

DESCRIPTION (provided by applicant): Immunosenescence starts from thymic involution, while age-related thymic involution results from thymic microenvironment changes regulated by multiple genes. Our hypothesis is the aged atrophic thymus must show changes in molecular features and cellular profiles that are not currently known, and transcription factors regulating thymic microenvironment built up mostly by thymic epithelial cells might be involved in the aging-related thymic involution process. Our approach is to investigate the aged atrophic thymus molecular features and cellular profiles focusing on K5/K8 co-localization on thymic epithelial cells, TN.1 hematopoietic progenitor cell subsets based on cKit and HAS expression, as well as the expression of two classes of Foxnl transcription; meanwhile test whether down regulation of the Foxn1 signal in medulla, cortex and total TECs in adult thymus can sufficiently induce aging-related thymic involution with site- and time- tissue-specific Cre-recombinase mouse model. These studies may ultimately lead to understanding the molecular mechanisms of age-related thymic involution and make possible strategies to reverse the function of the aged thymus.