Retinoblastoma cell-derived Twist protein promotes regulatory T cell development
Retinoblastoma cell-derived Twist protein promotes regulatory T cell development
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视网膜母细胞瘤细胞衍生的 Twist 蛋白可促进调节性 T 细胞发育。
DOI：
10.1007/s00262-020-02744-z
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发表时间：
2020-10-27
影响因子：
5.8
通讯作者：
Nie，Guohui
中科院分区：
文献类型：
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作者：
Zhang，Ruishi;Song，Yan-Nan;Nie，Guohui
背景肿瘤组织浸润性调节性T细胞（Treg）的发生发展尚不完全清楚。本研究探讨视网膜母细胞瘤细胞（retinoblastoma cell，Rbc）衍生的Twist相关蛋白1（Twist-related protein 1，Twist）在Treg发育中的作用。红细胞与CD 4 +T细胞培养，以评估红细胞衍生的Twist在Treggeneration.ResultsWe发现，超过90%的红细胞表达Twist的作用。Rb组织中Foxp 3 + TcB的表达与Rb细胞中Twist的表达呈正相关，与Rb患者的生存率和视力生存率呈负相关。低氧处理促进了Twist在细胞质、细胞核和细胞表面的表达。Twist通过结合TLR 4/髓样分化因子2复合物激活CD 4 +T细胞，并促进转化生长因子-β诱导的早期基因1产物和Foxp 3表达。结论Rbcs表达Twist，可诱导IL-4+ Foxp 3 + TcR，后者可抑制CD 8+细胞毒T细胞的活性。因此，Twist可能在Rb的发病机制中起重要作用。
BackgroundThe development of tumor tissue-infiltrating regulatory T cell (Treg) is incompletely understood. This study investigates the role of retinoblastoma cell (Rbc)-derived Twist‑related protein 1 (Twist) in the Treg development.MethodsThe surgically removed Rb tissues were collected. Rbcs were cultured with CD4+T cells to assess the role of Rbc-derived Twist in the Treg generation.ResultsWe found that more than 90% Rbcs expressed Twist. Foxp3+Tregs were detected in the Rb tissues that were positively correlated with the Twist expression in Rbcs, negatively associated with Rb patient survival and sight survival. Treating Rbcs with hypoxia promoted the Twist expression that could be detected in the cytoplasm, nuclei and on the cell surface. Twist activated CD4+T cells by binding the TLR4/myeloid differentiation factor 2 complex and promoted the transforming growth factor-β-inducible early gene 1 product and Foxp3 expression. These Rbc-induced Foxp3+Tregs showed immune-suppressive function on CD8+T cell proliferation.ConclusionsRbcs express Twist, that induces IL-4+Foxp3+Tregs; the latter can inhibit CD8+cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb.