转录因子T细胞β链在小鼠抗病毒CD8 T细胞SHIP-1中受微小RNA-155调控。

Hope Jennifer L, Stairiker Christopher J, Spantidea Panagiota I, Gracias Donald T, Carey Alison J, Fike Adam J, van Meurs Marjan, Brouwers-Haspels Inge, Rijsbergen Laurine C, Fraietta Joseph A, Mueller Yvonne M, Klop Rosemarieke C, Stelekati Erietta, Wherry E John, Erkeland Stefan J, Katsikis Peter D

Department of Immunology, Erasmus MC University Medical Center, Rotterdam, Netherlands.

Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States.

Front Immunol. 2017 Dec 6;8:1696. doi: 10.3389/fimmu.2017.01696. eCollection 2017.

We report here that the expression of the transcription factor T-bet, which is known to be required for effector cytotoxic CD8 T lymphocytes (CTL) generation and effector memory cell formation, is regulated in CTL by microRNA-155 (miR-155). Importantly, we show that the proliferative effect of miR-155 on CD8 T cells is mediated by T-bet. T-bet levels in CTL were controlled by miR-155 SH2 (Src homology 2)-containing inositol phosphatase-1 (SHIP-1), a known direct target of miR-155, and SHIP-1 directly downregulated T-bet. Our studies reveal an important and unexpected signaling axis between miR-155, T-bet, and SHIP-1 in CTL responses and suggest an important signaling module that regulates effector CTL immunity.

我们在此报告，转录因子T-bet的表达在细胞毒性CD8效应性T淋巴细胞（CTL）生成及效应性记忆细胞形成中是必需的，而在CTL中，其表达受微小RNA-155（miR-155）调控。重要的是，我们发现miR-155对CD8 T细胞的增殖作用是由T-bet介导的。CTL中的T-bet水平由miR-155的已知直接靶点含Src同源2结构域的肌醇磷酸酶-1（SHIP-1）控制，且SHIP-1直接下调T-bet。我们的研究揭示了CTL反应中miR-155、T-bet和SHIP-1之间重要且意外的信号轴，并提示了一个调节效应性CTL免疫的重要信号模块。