Differences in Expression Level of Helios and Neuropilin-1 Do Not Distinguish Thymus-Derived from Extrathymically-Induced CD4+Foxp3+ Regulatory T Cells.
Differences in Expression Level of Helios and Neuropilin-1 Do Not Distinguish Thymus-Derived from Extrathymically-Induced CD4+Foxp3+ Regulatory T Cells.
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Helios和Neuropilin-1表达水平的差异不会区分胸腺外诱导的CD4+ FOXP3+调节性T细胞。
DOI：
10.1371/journal.pone.0141161
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ignatowicz L
中科院分区：
文献类型：
--
作者：
Szurek E;Cebula A;Wojciech L;Pietrzak M;Rempala G;Kisielow P;Ignatowicz L
Helios转录因子和脑信号蛋白受体Nrp-1最初被描述为在胸腺内起源的CD 4 + Foxp 3 + T调节细胞（tTcR）上以高水平组成性表达。另一方面，据报道，在外周产生的（pT细胞）或离体诱导的（iT细胞）CD 4 + Foxp 3 + T细胞表达低水平的Helios和Nrp-1。不久之后，Nrp-1和Helios作为区分tTdR和pTdR的标记的可靠性受到质疑，直到现在还没有达成共识。在这里，我们使用了几种基因修饰的小鼠品系，有利于pT细胞或tT细胞的形成，并分析了这些细胞的TCR库。我们发现，具有可变水平的Nrp-1和Helios的TcR在支持tTcR或pTcR的自然分化的能力受损的小鼠中是丰富的。我们还报道了表达高或低水平Nrp-1或Helios的Treg克隆的TCR库与CD 4 + Foxp 3+的库相似，并且比CD 4 + Foxp 3-胸腺细胞的库更相似。这些结果表明，Nrp-1或Helios的高表达与低表达不能明确鉴定胸腺或外周来源的Treg克隆。
Helios transcription factor and semaphorin receptor Nrp-1 were originally described as constitutively expressed at high levels on CD4+Foxp3+ T regulatory cells of intrathymic origin (tTregs). On the other hand, CD4+Foxp3+ Tregs generated in the periphery (pTregs) or induced ex vivo (iTregs) were reported to express low levels of Helios and Nrp-1. Soon afterwards the reliability of Nrp-1 and Helios as markers discriminating between tTregs and pTregs was questioned and until now no consensus has been reached. Here, we used several genetically modified mouse strains that favor pTregs or tTregs formation and analyzed the TCR repertoire of these cells. We found that Tregs with variable levels of Nrp-1 and Helios were abundant in mice with compromised ability to support natural differentiation of tTregs or pTregs. We also report that TCR repertoires of Treg clones expressing high or low levels of Nrp-1 or Helios are similar and more alike repertoire of CD4+Foxp3+ than repertoire of CD4+Foxp3- thymocytes. These results show that high vs. low expression of Nrp-1 or Helios does not unequivocally identify Treg clones of thymic or peripheral origin.