小柯机器人

美国圣犹大儿童研究医院Yongqiang Feng、斯隆凯特琳肿瘤研究中心Alexander Y. Rudensky等研究人员合作发现，远端Foxp3增强子可实现依赖白介素2的胸腺Treg细胞谱系，从而实现强大的免疫耐受性。相关论文于2021年4月9日在线发表在《免疫》杂志上。

研究人员发现，在Foxp3诱导过程中白细胞介素2（IL-2）-STAT5信号转导于增强子（CNS0）上。CNS0促进了胸腺中IL-2依赖的CD25⁺Foxp3^–前体细胞向Treg细胞的过渡。它的缺乏导致新生儿Treg细胞生成受损，并随着年龄的增长而部分缓解。虽然由CNS0缺乏引起的胸腺Treg细胞缺乏并不能单独导致自身免疫，但是却加剧了由Aire基因破坏引起的自身免疫表现。因此，CNS0增强子的活性可确保在出生后早期就使Treg细胞稳定分化，并与其他耐受机制配合使自身免疫减至最小。

据悉，IL-2受体下游STAT5转录因子的激活诱导Foxp3的表达，这是Treg分化的关键步骤。由于IL-2R信号的多效性作用，目前尚不清楚STAT5如何直接作用于Foxp3基因座来促进其表达。

附：英文原文

Title: A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance

Author: Stanislav Dikiy, Jun Li, Lu Bai, Menglin Jiang, Laura Janke, Xinying Zong, Xiaolei Hao, Beatrice Hoyos, Zhong-Min Wang, Beisi Xu, Yiping Fan, Alexander Y. Rudensky, Yongqiang Feng

Issue&Volume: 2021-04-09

Abstract: Activation of the STAT5 transcription factor downstream of the Interleukin-2 receptor(IL-2R) induces expression of Foxp3, a critical step in the differentiation of regulatory T (Treg) cells. Due to thepleiotropic effects of IL-2R signaling, it is unclear how STAT5 acts directly on theFoxp3 locus to promote its expression. Here, we report that IL-2 – STAT5 signaling convergedon an enhancer (CNS0) during Foxp3 induction. CNS0 facilitated the IL-2 dependent CD25+Foxp3– precursor to Treg cell transition in the thymus. Its deficiency resulted in impairedTreg cell generation in neonates, which was partially mitigated with age. While thethymic Treg cell paucity caused by CNS0 deficiency did not result in autoimmunityon its own, it exacerbated autoimmune manifestations caused by disruption of the Aire gene. Thus, CNS0 enhancer activity ensures robust Treg cell differentiation earlyin postnatal life and cooperatively with other tolerance mechanisms minimizes autoimmunity.

DOI: 10.1016/j.immuni.2021.03.020

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00132-1

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