Sun Lina, Li Hongran, Luo Haiying, Zhao Yong
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beichen Xi Road 1-5, Chaoyang District, Beijing 100101, China.
Biomed Res Int. 2014;2014:206929. doi: 10.1155/2014/206929. Epub 2014 Feb 3.
Thymic epithelial cells (TECs) are the key components in thymic microenvironment for T cells development. TECs, composed of cortical and medullary TECs, are derived from a common bipotent progenitor and undergo a stepwise development controlled by multiple levels of signals to be functionally mature for supporting thymocyte development. Tumor necrosis factor receptor (TNFR) family members including the receptor activator for NF κ B (RANK), CD40, and lymphotoxin β receptor (LT β R) cooperatively control the thymic medullary microenvironment and self-tolerance establishment. In addition, fibroblast growth factors (FGFs), Wnt, and Notch signals are essential for establishment of functional thymic microenvironment. Transcription factors Foxn1 and autoimmune regulator (Aire) are powerful modulators of TEC development, differentiation, and self-tolerance. Dysfunction in thymic microenvironment including defects of TEC and thymocyte development would cause physiological disorders such as tumor, infectious diseases, and autoimmune diseases. In the present review, we will summarize our current understanding on TEC development and the underlying molecular signals pathways and the involvement of thymus dysfunction in human diseases.
胸腺上皮细胞（TECs）是胸腺微环境中T细胞发育的关键组成部分。TECs由皮质TECs和髓质TECs组成，起源于一个共同的双能祖细胞，并在多种信号的控制下逐步发育，以在功能上成熟从而支持胸腺细胞发育。肿瘤坏死因子受体（TNFR）家族成员，包括核因子κB受体激活剂（RANK）、CD40和淋巴毒素β受体（LTβR），共同控制胸腺髓质微环境和自身耐受性的建立。此外，成纤维细胞生长因子（FGFs）、Wnt和Notch信号对于功能性胸腺微环境的建立至关重要。转录因子Foxn1和自身免疫调节因子（Aire）是TEC发育、分化和自身耐受性的强大调节因子。胸腺微环境功能障碍，包括TEC和胸腺细胞发育缺陷，会导致诸如肿瘤、传染病和自身免疫性疾病等生理紊乱。在本综述中，我们将总结目前对TEC发育、潜在分子信号通路以及胸腺功能障碍在人类疾病中的作用的理解。
