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首页> 外文期刊>Cellular immunology >Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+thymocyte stage
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Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+thymocyte stage

机译:表观遗传和转录分析支持在CD4 + CD8 +胸腺细胞阶段的人体调节性T细胞承诺

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The natural CD25 + FOXP3 + regulatory T cell (Treg) population is generated as a distinct lineage in the thymus, but the details of Treg development in humans remain unclear, and the timing of Treg commitment is also contested. Here we have analyzed the emergence of CD25 + cells at the CD4 + CD8 + double positive (DP) stage in the human thymus. We show that these cells share T cell receptor repertoire with CD25 + CD4 single-positive thymocytes, believed to be committed Tregs. They already have a fully demethylated FOXP3 enhancer region and thus display stable expression of FOXP3 and the associated Treg phenotype. Transcriptome analysis also grouped the DP CD25 + and CD4 CD25 + thymocytes apart from the CD25 - subsets. Together with earlier studies, our data are consistent with human Treg commitment already at the DP thymocyte stage. We suggest that the most important antigens and signals necessary for human Treg differentiation may be found in the thymic cortex.
机译:天然CD25 + Foxp3 +调节性T细胞(Treg)群体被产生为胸腺中的不同谱系,但人类Treg发育的细节仍然不明确,而Treg承诺的时间也得到了争议。 在这里,我们在人胸腺中分析了CD4 + CD8 +双阳性(DP)阶段的CD25 +细胞的出现。 我们表明,这些细胞与CD25 + CD4单阳性胸腺细胞共享T细胞受体曲目,被认为是承诺的Tregs。 它们已经具有完全去甲基化的Foxp3增强区区域,从而显示出FoxP3和相关的Treg表型的稳定表达。 转录组分析还将DP CD25 +和CD4 CD25 +胸腺细胞与CD25 - 亚群分组。 与早期的研究一起,我们的数据与已经在DP胸腺细胞阶段的人类Treg承诺一致。 我们表明,可以在胸腺皮质中发现人Treg分化的最重要的抗原和信号。

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