SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells.
SATB1-dependent mitochondrial ROS production controls TCR signaling in CD4 T cells.
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DOI：
10.26508/lsa.202101093
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发表时间：
2021-11
影响因子：
4.4
通讯作者：
Kondo M
中科院分区：
文献类型：
--
作者：
Kuwabara T;Ishikawa F;Ikeda M;Ide T;Kohwi-Shigematsu T;Tanaka Y;Kondo M
SATB1通过线粒体转录因子A的表达调节线粒体功能和活性氧(ROS)的产生。SATB1介导的ROS的产生是TCR刺激和T细胞功能所必需的。特异的富含AT的序列结合蛋白-1(SATB1)定位于细胞核，重塑T细胞的染色质结构。SATB1缺陷的CD4T细胞不能对TCR刺激产生反应；然而，这种无反应的原因还有待阐明。在这里，我们证明了SATB1对于正常的线粒体功能是不可或缺的，并且是通过TCR激活CD4T细胞中的信号级联所必需的。幼稚SATB1缺陷的CD4T细胞比WT T细胞含有更少的线粒体，因为前者不表达线粒体转录因子A(TFAM)。SATB1缺乏的T细胞线粒体功能受损，通过结构性氧化破坏线粒体ROS的产生和SHP-1的失活。异位TFAM的表达增加了线粒体质量和线粒体ROS的产生，并挽救了SATB1缺陷T细胞中抗原特异性反应的缺陷。因此，SATB1通过调节TFAM的表达来维持线粒体的质量和功能是至关重要的，而TFAM是TCR信号转导所必需的。
SATB1 regulates mitochondrial function and reactive oxygen species (ROS) production through the expression of mitochondrial transcription factor A. SATB1-mediated ROS production is necessary for TCR stimulation and T-cell function. Special AT-rich sequence binding protein-1 (SATB1) is localized to the nucleus and remodels chromatin structure in T cells. SATB1-deficient CD4 T cells cannot respond to TCR stimulation; however, the cause of this unresponsiveness is to be clarified. Here, we demonstrate that SATB1 is indispensable to proper mitochondrial functioning and necessary for the activation of signal cascades via the TCR in CD4 T cells. Naïve SATB1-deficient CD4 T cells contain fewer mitochondria than WT T cells, as the former do not express mitochondrial transcription factor A (TFAM). Impaired mitochondrial function in SATB1-deficient T cells subverts mitochondrial ROS production and SHP-1 inactivation by constitutive oxidization. Ectopic TFAM expression increases mitochondrial mass and mitochondrial ROS production and rescues defects in the antigen-specific response in the SATB1-deficient T cells. Thus, SATB1 is vital for maintaining mitochondrial mass and function by regulating TFAM expression, which is necessary for TCR signaling.