Polypyrimidine Tract Binding Protein 1 regulates the activation of mouse CD8 T cells
Polypyrimidine Tract Binding Protein 1 regulates the activation of mouse CD8 T cells
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聚嘧啶束结合蛋白 1 调节小鼠 CD8 T 细胞的活化
DOI：
10.1101/2022.03.03.482829
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
D'Angeli V
中科院分区：
文献类型：
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作者：
D'Angeli V
人们发现 RNA 结合蛋白聚嘧啶束结合蛋白 1 (PTBP1) 在 CD4 T 细胞激活中发挥作用，但其在 CD8 T 细胞中的功能尚未测试。我们证明它对于幼稚小鼠 CD8 T 细胞的发育是可有可无的，但对于抗原特异性 CD8 T 细胞在体内最佳扩增和产生效应分子是必需的。 PTBP1 在调节幼稚 CD8 T 细胞激活后导致 IL-2 和 TNF 产生的早期事件中发挥重要作用。它还需要保护激活的 CD8 T 细胞免于凋亡。除了调节约 200 个 mRNA 的丰度外，PTBP1 还控制初始 CD8 T 细胞中 400 多个基因的选择性剪接。 c-Fos、NFATc2 和 NFATc3 的核积累需要 PTBP1，但 NFATc1 不需要。这种对 NFAT 蛋白的选择性作用与 PTBP1 促进的较短 Aβ1 异构体的表达以及钙调神经磷酸酶催化 A 亚基的外显子 13 跳过的 Aβ2 异构体的表达相关。这些发现揭示了 PTBP1 在调节 CD8 T 细胞激活中的关键作用。
The RNA‐binding protein polypyrimidine tract binding protein 1 (PTBP1) has been found to have roles in CD4 T‐cell activation, but its function in CD8 T cells remains untested. We show it is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen‐specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naïve CD8 T cell leading to IL‐2 and TNF production. It is also required to protect activated CD8 T cells from apoptosis. PTBP1 controls alternative splicing of over 400 genes in naïve CD8 T cells in addition to regulating the abundance of ∼200 mRNAs. PTBP1 is required for the nuclear accumulation of c‐Fos, NFATc2, and NFATc3, but not NFATc1. This selective effect on NFAT proteins correlates with PTBP1‐promoted expression of the shorter Aβ1 isoform and exon 13 skipped Aβ2 isoform of the catalytic A‐subunit of calcineurin phosphatase. These findings reveal a crucial role for PTBP1 in regulating CD8 T‐cell activation.