1. MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium.
- Author
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Zhang, Baojun, Liu, Si-Qi, Li, Chaoran, Lykken, Erik, Jiang, Shan, Wong, Elizabeth, Gong, Zhihua, Tao, Zhongfen, Zhu, Bo, Wan, Ying, and Li, Qi-Jing
- Subjects
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MICRORNA , *NECROSIS , *REACTIVE oxygen species , *T cell receptors , *CELLULAR signal transduction , *MITOCHONDRIA - Abstract
Summary Upon antigen engagement, augmented cytosolic reactive oxygen species (ROS) are needed to achieve optimal T cell receptor (TCR) signaling. However, uncontrolled ROS production is a prominent cause of necrosis, which elicits hyper-inflammation and tissue damage. Hence, it is critical to program activated T cells to achieve ROS equilibrium. Here, we determined that miR-23a is indispensable for effector CD4 + T cell expansion, particularly by providing early protection from excessive necrosis. Mechanistically, miR-23a targeted PPIF, gatekeeper of the mitochondria permeability transition pore, thereby restricting ROS flux and maintaining mitochondrial integrity. Upon acute Listeria monocytogenes infection, deleting miR-23a in T cells resulted in excessive inflammation, massive liver damage, and a marked mortality increase, which highlights the essential role of miR-23a in maintaining immune homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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