Yang Siyoung, Fujikado Noriyuki, Kolodin Dmitriy, Benoist Christophe, Mathis Diane
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, South Korea.
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Science. 2015 May 1;348(6234):589-94. doi: 10.1126/science.aaa7017. Epub 2015 Mar 19.
Aire is an important regulator of immunological tolerance, operating in a minute subset of thymic stromal cells to induce transcripts encoding peptides that guide T cell selection. Expression of Aire during a perinatal age window is necessary and sufficient to prevent the multiorgan autoimmunity characteristic of Aire-deficient mice. We report that Aire promotes the perinatal generation of a distinct compartment of Foxp3(+)CD4(+) regulatory T (Treg) cells, which stably persists in adult mice. This population has a role in maintaining self-tolerance, a transcriptome and an activation profile distinguishable from those of Tregs produced in adults. Underlying the distinct Treg populations are age-dependent, Aire-independent differences in the processing and presentation of thymic stromal-cell peptides, resulting in different T cell receptor repertoires. Our findings expand the notion of a developmentally layered immune system.
Aire是免疫耐受的重要调节因子，在一小部分胸腺基质细胞中发挥作用，诱导编码引导T细胞选择的肽段的转录本。围产期年龄窗口期间Aire的表达对于预防Aire缺陷小鼠的多器官自身免疫是必要且充分的。我们报告称，Aire促进了Foxp3(+)CD4(+)调节性T（Treg）细胞独特亚群的围产期生成，该亚群在成年小鼠中稳定存在。这群细胞在维持自身耐受方面发挥作用，其转录组和激活谱与成年期产生的Treg细胞不同。不同Treg细胞群体的基础是胸腺基质细胞肽段加工和呈递过程中与年龄相关、不依赖Aire的差异，从而导致不同的T细胞受体库。我们的发现扩展了发育分层免疫系统的概念。
