文章：

前列腺素E2通过Wnt/β-catenin途径促进初始UCBT细胞的存活，并改变UCBT后的免疫重建

Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/β-catenin pathway and alters immune reconstitution after UCBT

原文发布日期：2014-01-17

DOI: 10.1038/bcj.2013.75

类型: Original Article

开放获取: 是

英文摘要：

The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2Rβ, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/β-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8+ cells, these patients also had increased fractions of CD8+CD45RO-CD62L+ plus CD8+CD45RO+CD62L+ subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/β-catenin axis may have significant implications for harnessing immunity in the context of UCBT, where impaired immune reconstitution is associated with late memory T-cell skewing.

摘要翻译： 

脐带血移植（UCBT）的疗效因造血干细胞（HSC）剂量不足而受限，导致植入时间延长、免疫重建延迟以及晚期记忆T细胞偏向分化。将脐带血暴露于二甲前列腺素E2（dmPGE2）可增加体内HSC数量。我们发现dmPGE2通过修饰Wnt信号通路诱导脐带血T淋巴细胞产生T细胞因子（TCF）介导的转录。Wnt信号通路上调白细胞介素（IL）-7R和IL-2Rβ，进而通过稳态细胞因子IL-7和IL-15增强细胞存活。dmPGE2同时诱导Wnt通路组分及Wnt受体表达，从而 priming 脐带血T细胞在体内接收Wnt配体信号。我们观察到，接受PGE2处理脐带血移植的患者T细胞中Wnt转录因子TCF7及其靶标EOMES表达升高。与Wnt/β-连环蛋白信号诱导并维持初始T细胞、记忆前体细胞和长效中央记忆CD8+细胞的作用一致，这些患者体内包含这些T细胞群体的CD8+CD45RO-CD62L+及CD8+CD45RO+CD62L+亚群比例增加。PGE2/Wnt/β-连环蛋白轴的作用对于在UCBT中调控免疫具有重要意义——该移植背景下免疫重建受损与晚期记忆T细胞偏向分化密切相关。

原文链接：

Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/β-catenin pathway and alters immune reconstitution after UCBT