Abstract
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.
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Acknowledgements
We thank Dr J.Å. Gustafsson (Karolinska Institutet) for providing LXRα- and LXRβ-deficient mice. We thank Dr H.H. Xue (University of Iowa) for providing retroviral vectors. We thank the core facility center of Third Military Medical University for cell sorting. This work was supported by grants from the National Key Research and Development Program of China (No. 2016YFA0502203 to X.Z. and No. 2016YFA0502204 to Y.W.), the National Natural Science Foundation of China (No. 81571537 to T.Z., No. 31770949 to X.Z., No. 31770972 to Z.X., and No. 81571604 to J.Z.), and the Chongqing Basic and Frontier Research Project (No. cstc2015jcyjBX0086 to H.He.).
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H.Hu., X.W., and D.M. performed the experiments and analyzed the data with assistance from Y.F., L.Z., Z.L., S.T., X.L., and Y.Ca. X.Z., Y.W., T.Z., H.He., Z.X., and J.Z. procured several grants. Y.Ch. provided LXRα- and LXRβ-deficient mice. X.Z., H.Hu., and T.Z. designed the study. X.Z. and H.Hu. wrote the paper. X.Z., Y.W., and T.Z. supervised the study.
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Huang, H., Wu, X., Meng, D. et al. Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression. Cell Mol Immunol 18, 1969–1980 (2021). https://doi.org/10.1038/s41423-020-00546-y
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DOI: https://doi.org/10.1038/s41423-020-00546-y
