当前位置: X-MOL 学术Cell. Mol. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression.
Cellular & Molecular Immunology ( IF 24.1 ) Pub Date : 2020-09-22 , DOI: 10.1038/s41423-020-00546-y
Huang Huang 1 , Xiaoping Wu 1, 2 , Dongwei Meng 1 , Yizhou Feng 3 , Lan Zhou 1 , Zhenyu Liu 4 , Shupei Tang 5 , Xueqin Li 4 , Yi Cao 1 , Haiyang He 1 , Zhunyi Xie 1 , Jingbo Zhang 4 , Yongwen Chen 1 , Tingting Zhao 1 , Yuzhang Wu 1 , Xinyuan Zhou 1
Affiliation  

Liver X receptors (LXRs) are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation. However, whether LXRs play a role in thymocyte development remains largely unknown. Here, we demonstrated that LXRβ deficiency caused a reduction in single-positive (SP) thymocytes, whereas the transitions from the double-negative to SP stage were normal. Meanwhile, LXRβ-null SP thymocytes exhibited increased apoptosis and impairment of the IL-7Rα-Bcl2 axis. In addition, the LXR agonist T0901317 promoted the survival of SP thymocytes with enhanced IL-7Rα expression in wild-type mice but not in LXRβ-deficient mice. Mechanistically, LXRβ positively regulated the expression of IL-7Rα via direct binding to the Il7r allele in SP thymocytes, and forced expression of IL-7Rα or Bcl2 restored the survival of LXRβ-defective SP thymocytes. Thus, our results indicate that LXRβ functions as an important transcription factor upstream of IL-7Rα to promote the survival of SP thymocytes.



中文翻译:

肝脏 X 受体 β 通过调节 IL-7Rα 表达是单阳性胸腺细胞存活所必需的。

肝脏 X 受体 (LXR) 被称为脂质代谢中的关键转录因子,据报道在 T 细胞增殖中起重要作用。然而,LXRs 是否在胸腺细胞发育中起作用仍然很大程度上未知。在这里,我们证明 LXRβ 缺乏导致单阳性 (SP) 胸腺细胞减少,而从双阴性到 SP 阶段的转变是正常的。同时,LXRβ-null SP 胸腺细胞表现出细胞凋亡增加和 IL-7Rα-Bcl2 轴受损。此外,LXR 激动剂 T0901317 促进了 SP 胸腺细胞的存活,在野生型小鼠中 IL-7Rα 表达增强,但在 LXRβ 缺陷小鼠中没有。从机制上讲,LXRβ 通过直接结合 Il7r 正向调节 IL-7Rα 的表达SP 胸腺细胞中的等位基因和 IL-7Rα 或 Bcl2 的强制表达恢复了 LXRβ 缺陷型 SP 胸腺细胞的存活。因此,我们的结果表明LXRβ作为IL-7Rα上游的重要转录因子发挥作用,以促进SP胸腺细胞的存活。

更新日期:2020-09-22
down
wechat
bug