Cunningham Cody A, Cardwell Leah N, Guan Yue, Teixeiro Emma, Daniels Mark A
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212
J Immunol. 2016 May 15;196(10):4003-13. doi: 10.4049/jimmunol.1501728. Epub 2016 Apr 15.
The scaffold molecule POSH is crucial for the regulation of proliferation and effector function in CD8(+) T cells. However, its role in CD4(+) T cells is not known. In this study, we found that disruption of the POSH scaffold complex established a transcriptional profile that strongly skewed differentiation toward Th2, led to decreased survival, and had no effect on cell cycle entry. This is in stark contrast to CD8(+) T cells in which POSH regulates cell cycle and does not affect survival. Disruption of POSH in CD4(+) T cells resulted in the loss of Tak1-dependent activation of JNK1/2 and Tak1-mediated survival. However, in CD8(+) T cells, POSH regulates only JNK1. Remarkably, each type of T cell had a unique composition of the POSH scaffold complex and distinct posttranslational modifications of POSH. These data indicate that the mechanism that regulates POSH function in CD4(+) T cells is different from CD8(+) T cells. All together, these data strongly suggest that POSH is essential for the integration of cell-type-specific signals that regulate the differentiation, survival, and function of T cells.
支架分子POSH对CD8(+) T细胞的增殖调控和效应功能至关重要。然而，其在CD4(+) T细胞中的作用尚不清楚。在本研究中，我们发现破坏POSH支架复合物会建立一种转录谱，该转录谱强烈偏向Th2分化，导致存活率降低，且对细胞周期进入无影响。这与CD8(+) T细胞形成鲜明对比，在CD8(+) T细胞中，POSH调节细胞周期且不影响存活。CD4(+) T细胞中POSH的破坏导致Tak1依赖的JNK1/2激活丧失以及Tak1介导的存活丧失。然而，在CD8(+) T细胞中，POSH仅调节JNK1。值得注意的是，每种类型的T细胞都有独特的POSH支架复合物组成以及POSH不同的翻译后修饰。这些数据表明，调节CD4(+) T细胞中POSH功能的机制与CD8(+) T细胞不同。总之，这些数据强烈表明，POSH对于整合调节T细胞分化、存活和功能的细胞类型特异性信号至关重要。
