Splicing factor SRSF1 is essential for CD8 T cell function and host antigen-specific viral immunity.
Splicing factor SRSF1 is essential for CD8 T cell function and host antigen-specific viral immunity.
复制标题
DOI：
10.3389/fimmu.2022.906355
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞毒性CD8T细胞在宿主对病毒病原体的抗原特异性免疫反应中起关键作用。在这里，我们报告了富含丝氨酸/精氨酸的剪接因子(SRSF)1在CD8T细胞稳态和功能中的重要作用。具体地说，SRSF1对于维持淋巴间隔内正常的CD8T淋巴细胞数量，以及CD8T细胞的增殖能力和细胞毒功能是必要的。此外，在小鼠的病毒感染挑战中，SRSF1是抗原特异性干扰素-γ细胞因子反应所必需的。对SRSF1缺陷的T细胞的转录组学分析表明，SRSF1控制着增殖、MAP激酶信号和干扰素信号通路。在分子水平上，SRSF1调控着Mnk2/p38-MAPK轴的表达和活性。我们的发现揭示了以前未知的SRSF1在细胞毒性CD8 T淋巴细胞的生理和功能中的作用，以及在病毒免疫发病机制中的潜在分子机制。
Cytotoxic CD8 T cells are crucial for the host antigen-specific immune response to viral pathogens. Here we report the identification of an essential role for the serine/arginine-rich splicing factor (SRSF) 1 in CD8 T cell homeostasis and function. Specifically, SRSF1 is necessary for the maintenance of normal CD8 T lymphocyte numbers in the lymphoid compartment, and for the proliferative capacity and cytotoxic function of CD8 T cells. Furthermore, SRSF1 is required for antigen-specific IFN-γ cytokine responses in a viral infection challenge in mice. Transcriptomics analyses of Srsf1-deficient T cells reveal that SRSF1 controls proliferation, MAP kinase signaling and IFN signaling pathways. Mechanistically, SRSF1 controls the expression and activity of the Mnk2/p38-MAPK axis at the molecular level. Our findings reveal previously unrecognized roles for SRSF1 in the physiology and function of cytotoxic CD8 T lymphocytes and a potential molecular mechanism in viral immunopathogenesis.