Impaired Autophagy and Defective T Cell Homeostasis in Mice with T Cell-Specific Deletion of Receptor for Activated C Kinase 1.
Impaired Autophagy and Defective T Cell Homeostasis in Mice with T Cell-Specific Deletion of Receptor for Activated C Kinase 1.
复制标题
T 细胞特异性删除活化 C 激酶 1 受体导致小鼠自噬受损和 T 细胞稳态缺陷
DOI：
10.3389/fimmu.2017.00575
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发表时间：
2017
影响因子：
7.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Qiu G;Liu J;Cheng Q;Wang Q;Jing Z;Pei Y;Zhao M;Wang J;Guo JY;Zhang J
自噬在维持T细胞动态平衡中起着核心作用。我们以前的研究表明，肝细胞特异性的活化C激酶1受体(RACK1)缺陷会导致肝脏中的脂质堆积，并伴有自噬功能受损，但其在T细胞中的作用尚不清楚。在这里，我们报告了T细胞特异性RACK1缺失的小鼠表现出胸腺内常规T细胞和调节性T(Treg)细胞的正常发育，但外周血中CD4+和CD8+T细胞的数量减少。这些缺陷是细胞固有的，线粒体清除受损，对细胞死亡的敏感性增加，增殖减少，这可以用自噬受损来解释。此外，RACK1对于恒定的自然T细胞发育是必不可少的。在体内，T细胞特异性RACK1的缺失抑制刀豆蛋白A诱导的急性肝损伤。我们的数据表明，RACK1是T细胞内稳态的关键调节因子。
Autophagy plays a central role in maintaining T cell homeostasis. Our previous study has shown that hepatocyte-specific deficiency of receptor for activated C kinase 1 (RACK1) leads to lipid accumulation in the liver, accompanied by impaired autophagy, but its in vivo role in T cells remains unclear. Here, we report that mice with T cell-specific deletion of RACK1 exhibit normal intrathymic development of conventional T cells and regulatory T (Treg) cells but reduced numbers of peripheral CD4+ and CD8+ T cells. Such defects are cell intrinsic with impaired mitochondrial clearance, increased sensitivity to cell death, and decreased proliferation that could be explained by impaired autophagy. Furthermore, RACK1 is essential for invariant natural T cell development. In vivo, T cell-specific loss of RACK1 dampens concanavalin A-induced acute liver injury. Our data suggest that RACK1 is a key regulator of T cell homeostasis.