The transcription factor Foxp1 preserves integrity of an active Foxp3 locus in extrathymic Treg cells.,Nature Communications

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The transcription factor Foxp1 preserves integrity of an active Foxp3 locus in extrathymic Treg cells.
Nature Communications ( IF 14.7 ) Pub Date : 2018-10-26 , DOI: 10.1038/s41467-018-07018-y
Sayantani Ghosh _{1,

2} , Sinchita Roy-Chowdhuri ₃ , Keunsoo Kang ₄ , Sin-Hyeog Im _{1,

2} , Dipayan Rudra _{1,

2}

Affiliation

Regulatory T (Treg) cells, which are broadly classified as thymically derived (tTreg) or extrathymically induced (iTreg), suppress immune responses and display stringent dependence to the transcription factor Foxp3. However precise understanding of molecular events that promote and preserve Foxp3 expression in Treg cells is still evolving. Here we show that Foxp1, a forkhead transcription factor and a sibling family member of Foxp3, is essential for sustaining optimal expression of Foxp3 specifically in iTreg cells. Deletion of Foxp1 renders iTreg cells to gradually lose Foxp3, resulting in dramatically reduced Nrp1^-Helios^- iTreg compartment as well as augmented intestinal inflammation in aged mice. Our finding underscores a mechanistic module in which evolutionarily related transcription factors establish a molecular program to ensure efficient immune homeostasis. Furthermore, it provides a novel target that can be potentially modulated to exclusively reinforce iTreg stability keeping their thymic counterpart unperturbed.

中文翻译：

转录因子 Foxp1 保留了胸腺外 Treg 细胞中活性 Foxp3 基因座的完整性。

调节性 T (Treg) 细胞大致分为胸腺来源的 (tTreg) 或胸腺外诱导的 (iTreg)，它们抑制免疫反应并表现出对转录因子 Foxp3 的严格依赖性。然而，对促进和维持 Treg 细胞中 Foxp3 表达的分子事件的精确理解仍在不断发展。在这里，我们表明 Foxp1 是一种叉头转录因子，也是 Foxp3 的兄弟家族成员，对于维持 Foxp3 特别是在 iTreg 细胞中的最佳表达至关重要。 Foxp1的缺失使iTreg细胞逐渐失去Foxp3，导致Nrp1 ^- Helios ^- iTreg区室显着减少，并加剧老年小鼠的肠道炎症。我们的发现强调了一个机制模块，其中进化相关的转录因子建立了一个分子程序以确保有效的免疫稳态。此外，它提供了一个新的靶点，可以通过潜在的调节来专门增强 iTreg 的稳定性，从而保持其胸腺对应物不受干扰。

更新日期：2018-10-26

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