Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression

Autor: Zhunyi Xie, Tingting Zhao, Zhenyu Liu, Dongwei Meng, Yi Cao, Yuzhang Wu, Jingbo Zhang, Huang Huang, Xiaoping Wu, Shupei Tang, Haiyang He, Xueqin Li, Yongwen Chen, Xinyuan Zhou, Yizhou Feng, Lan Zhou
Rok vydání: 2020
Předmět:
Zdroj: Cell Mol Immunol
ISSN: 2042-0226
1672-7681
DOI: 10.1038/s41423-020-00546-y
Popis: 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.
Databáze: OpenAIRE
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