机构:[1]Institute of Immunology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China[2]Institute for Cancer Medicine and School of BasicMedical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, China[3]Chengdu No. 7 Wanda High School, Chengdu, Sichuan 610036, China[4]Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China[5]Department of Urology, Xinqiao Hospital, Third Military Medical University,Chongqing 400038, China
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.
基金:
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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外文
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出版当年[2021]版:
大类|1 区医学
小类|1 区免疫学
最新[2023]版:
大类|1 区医学
小类|1 区免疫学
第一作者:
第一作者机构:[1]Institute of Immunology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China
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推荐引用方式(GB/T 7714):
Huang Huang,Xiaoping Wu,Dongwei Meng,et al.Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression.[J].Cellular & Molecular Immunology.2021,18(8):1969-1980.doi:10.1038/s41423-020-00546-y.
APA:
Huang Huang,Xiaoping Wu,Dongwei Meng,Yizhou Feng,Lan Zhou...&Xinyuan Zhou.(2021).Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression..Cellular & Molecular Immunology,18,(8)
MLA:
Huang Huang,et al."Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression.".Cellular & Molecular Immunology 18..8(2021):1969-1980