Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Trends Immunol. 2022 Oct;43(10):782-791. doi: 10.1016/j.it.2022.07.010. Epub 2022 Aug 22.
Medullary thymic epithelial cells (mTECs) clonally delete or divert autoreactive T cells by ectopically expressing a diverse array of peripheral-tissue antigens (PTAs) within the thymus. Although thymic stromal cells with histological features of extra-thymic cell types, like myocytes or neurons, have been observed by light microscopy since the mid-1800s, most modern work on PTA expression has focused on the transcription factor Aire. Here, we highlight recent work that has refocused attention on such 'misplaced' thymic cells, referred to collectively as thymic mimetic cells. We review the molecular underpinnings of mimetic cells and their roles in establishing T cell tolerance, and we propose that mimetic cells play important roles in autoimmunity. Finally, we suggest future directions for this emerging area.
髓质胸腺上皮细胞 (mTEC) 通过在胸腺内异位表达多种外周组织抗原 (PTA) 来克隆性删除或改变自身反应性 T 细胞。尽管自 19 世纪中叶以来，通过光学显微镜已经观察到具有胸腺外细胞类型（如肌细胞或神经元）组织学特征的胸腺基质细胞，但大多数关于 PTA 表达的现代研究都集中在转录因子 Aire 上。在这里，我们重点介绍了最近的研究工作，这些工作重新关注了此类“错位”的胸腺细胞，统称为胸腺模拟细胞。我们回顾了模拟细胞的分子基础及其在建立 T 细胞耐受中的作用，并提出模拟细胞在自身免疫中起重要作用。最后，我们为这一新兴领域提出了未来的发展方向。
