胸腺增龄性萎缩过程中淋巴造血祖细胞和胸腺基质细胞相互作用机制研究

Thymus is the place where T-lymphocytes develope and mature. Thymic atrophy occurs along with aging. Age-related thymic involution causes T-lymphocyte abnormity in quality and volume, and results in the senescence of immune system and increases the risk of suffering from cancer, autoimmune diseases and pathogenic infection, such as viruses and bacterials in the aged. The mechanism of age-related thymic involution is not clear until now. Thymic transcription factors, cytokines and other factors may involve in the process of adjusting involution. Based on previous studies, this project will analyze the mechanism of the interaction between lymphohematopoietic cell and thymic stromal cell during the thymic aging by a special model of competition development, and study the effects of Notch signal and microRNA regulation on the thymic aging. It will be known whether and when the defects of lymphohematopoietic cell of the aged occur and that the Notch signal and microRNA regulation function during the thymic aging. The study above provides the basis of theory and experiment for knowing age-related thymic involution further, inceasing immune function and life span of the aged.

胸腺是T淋巴细胞发育场所, 随年龄增长出现萎缩，萎缩受体内激素变化影响。胸腺增龄性萎缩影响T淋巴细胞的发育, 造成外周T淋巴细胞质与量的异常，引起免疫衰老，增加了老年人罹患癌症、自身免疫性疾病及病毒、细菌等病原感染的危险。胸腺增龄性萎缩的发生分子机制尚不完全清楚。我们最近的研究发现随年龄增长胸腺基质细胞（TSC）出现增殖能力下降、凋亡率增加和末梢免疫幼稚T细胞减少、效应/记忆T细胞增加。本项目通过独特的体内竞争发育实验模型进一步研究萎缩过程中淋巴造血祖细胞（LPC）与TSC的异常相互作用以及萎缩过程中Notch信号和miRNA的调节机制,明确老龄的LPC是否和在何时出现内在的不可逆的缺陷，明确Notch信号和相关miRNA在胸腺增龄性萎缩过程中的作用。研究结果将有助于深入理解胸腺增龄性萎缩分子调节机制，为进一步认识胸腺老化、预防和延迟衰老、提高老龄人口健康水平提供实验基础和理论依据。

胸腺是T淋巴细胞发育场所, 随年龄增长出现萎缩，萎缩受体内激素变化影响。胸腺增龄性萎缩影响T淋巴细胞的发育, 造成外周T淋巴细胞质与量的异常，引起免疫衰老，增加了老年人罹患癌症、自身免疫性疾病及病毒、细菌等病原感染的危险。胸腺增龄性萎缩的发生分子机制尚不完全清楚。我们最近的研究发现随年龄增长胸腺基质细胞（TSC）出现增值能力下降、凋亡率增加和末梢免疫幼稚T细胞减少、效应/记忆T细胞增加。本项目通过独特的体内竞争发育实验模型进一步研究萎缩过程中淋巴造血祖细胞（LPC）与TSC的异常相互作用以及胸腺发育相关的Notch信号和miRNA调节机制,明确了老龄的LPC是否和在何时出现内在的不可逆的缺陷，明确了Notch信号和相关miRNA在胸腺增龄性萎缩过程中发挥的作用。研究结果将有助于深入理解胸腺增龄性萎缩分子调节机制，为进一步认识胸腺老化、预防和延迟衰老，提高老龄人口健康水平提供实验基础和理论依据