Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Trends Immunol. 2017 Nov;38(11):805-816. doi: 10.1016/j.it.2017.07.010. Epub 2017 Aug 19.
T cells undergo positive and negative selection in the thymic cortex and medulla, respectively. A promiscuous expression of a wide array of self-antigens in the thymus is essential for the negative selection of self-reactive T cells and the establishment of central tolerance. Aire was originally thought to be the exclusive factor regulating the expression of tissue-restricted antigens, but Fezf2 recently emerged as a critical transcription factor in this regulatory activity. Fezf2 is selectively expressed in thymic medullary epithelial cells, regulates a large number of tissue-restricted antigens and suppresses the onset of autoimmune responses. Here, we discuss novel findings on the transcriptional mechanisms of tissue restricted-antigen expression in the medullary thymic epithelial cells and its effects on T cell selection.
T 细胞分别在胸腺皮质和髓质中经历阳性选择和阴性选择。在胸腺中广泛表达多种自身抗原对于自身反应性 T 细胞的阴性选择和中枢耐受的建立是必不可少的。Aire 最初被认为是调节组织特异性抗原表达的唯一因素，但 Fezf2 最近成为这种调节活性中的关键转录因子。Fezf2 选择性地在胸腺髓质上皮细胞中表达，调节大量组织特异性抗原，并抑制自身免疫反应的发生。在这里，我们讨论了关于髓质胸腺上皮细胞中组织特异性抗原表达的转录机制及其对 T 细胞选择的影响的新发现。
