Helios+ and Helios- Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires.,European Journal of Immunology

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Helios+ and Helios- Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2019-01-15 , DOI: 10.1002/eji.201847935
Angela M Thornton ₁ , Jinghua Lu ₂ , Patricia E Korty ₁ , Yong Chan Kim ₁ , Craig Martens ₃ , Peter D Sun ₂ , Ethan M Shevach ₁

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The transcription factor Helios is expressed in a large subset of Foxp3+ Tregs. We previously proposed that Helios is a marker of thymic derived Treg (tTreg), while Helios- Treg were induced from Foxp3- T conventional (Tconv) cells in the periphery (pTreg). To compare the two Treg subpopulations, we generated Helios-GFP reporter mice and crossed them to Foxp3-RFP reporter mice. The Helios+ Treg population expressed a more activated phenotype, had a slightly higher suppressive capacity in vitro and expressed a more highly demethylated TSDR but were equivalent in their ability to suppress inflammatory bowel disease in vivo. However, Helios+ Treg more effectively inhibited the proliferation of activated, autoreactive splenocytes from scurfy mice. When Helios+ and Helios- Treg were transferred to lymphoreplete mice, both populations maintained comparable Foxp3 expression, but Foxp3 expression was less stable in Helios- Treg when transferred to lymphopenic mice. Gene expression profiling demonstrated a large number of differentially expressed genes and showed that Helios- Treg expressed certain genes normally expressed in CD4+ Foxp3- T cells. TCR repertoire analysis indicated very little overlap between Helios+ and Helios- Treg. Thus, Helios+ and Helios- Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires.

中文翻译：

Helios +和Helios- Treg亚群在表型和功能上是不同的，并表达不同的TCR库。

转录因子Helios在Foxp3 + Treg的很大一部分中表达。我们以前提出Helios是胸腺来源的Treg（tTreg）的标志物，而Helios-Treg是由外周的Foxp3-T常规（Tconv）细胞（pTreg）诱导的。为了比较两个Treg亚群，我们生成了Helios-GFP报告基因小鼠，并将它们与Foxp3-RFP报告基因小鼠杂交。Helios + Treg群体表现出更高的激活表型，体外抑制能力略高，TSDR甲基化程度更高，但在体内抑制炎症性肠病的能力相当。但是，Helios + Treg更有效地抑制了来自毛茸茸的小鼠的活化的自反应性脾细胞的增殖。当将Helios +和Helios-Treg转移至淋巴完全性小鼠时，两种种群都维持了可比的Foxp3表达，但是当转移到淋巴细胞减少小鼠中时，Helios-Treg中的Foxp3表达不稳定。基因表达谱显示了许多差异表达的基因，并表明Helios-Treg表达了通常在CD4 + Foxp3-T细胞中表达的某些基因。TCR库分析表明，Helios +和Helios-Treg之间几乎没有重叠。因此，Helios +和Helios-Treg亚群在表型和功能上是不同的，并且表达不同的TCR库。TCR库分析表明，Helios +和Helios-Treg之间几乎没有重叠。因此，Helios +和Helios-Treg亚群在表型和功能上是不同的，并且表达不同的TCR库。TCR库分析表明，Helios +和Helios-Treg之间几乎没有重叠。因此，Helios +和Helios-Treg亚群在表型和功能上是不同的，并且表达不同的TCR库。

更新日期：2019-01-15

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