Liver X receptor beta is required for the survival of single-positive thymocytes by regulating IL-7R alpha expression
Liver X receptor beta is required for the survival of single-positive thymocytes by regulating IL-7R alpha expression
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肝脏 X 受体 β 通过调节 IL-7R α 表达来维持单阳性胸腺细胞的存活
DOI：
10.1038/s41423-020-00546-y
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发表时间：
2021
影响因子：
24.1
通讯作者：
Zhou Xinyuan
中科院分区：
文献类型：
--
作者：
Huang Huang;Wu Xiaoping;Meng Dongwei;Feng Yizhou;Zhou Lan;Liu Zhenyu;Tang Shupei;Li Xueqin;Cao Yi;He Haiyang;Xie Zhunyi;Zhang Jingbo;Chen Yongwen;Zhao Tingting;Wu Yuzhang;Zhou Xinyuan
肝脏X受体（LXRs）是脂质代谢中的关键转录因子，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发挥作用仍然是未知的。在这里，我们证明了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胸腺细胞表现出凋亡增加和IL-7 R α-Bcl 2轴受损。此外，在野生型小鼠中，LXR激动剂T0901317促进SP胸腺细胞的存活，并增强IL-7 R α表达，但在LXRβ缺陷型小鼠中则不然。LXRβ通过与IL-7 r等位基因直接结合，正性调节IL-7 R α的表达，而IL-7 R α或Bcl-2的强制表达可恢复LXRβ缺陷的SP胸腺细胞的存活。因此，我们的研究结果表明，LXRβ作为一个重要的转录因子上游的IL-7 R α促进SP胸腺细胞的存活。
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 theIl7rallele 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.