Liver X receptorβis required for the survival of single-positive thymocytes by regulating IL-7Rαexpression  

作　　者：Huang Huang Xiaoping Wu Dongwei Meng Yizhou Feng Lan Zhou Zhenyu Liu Shupei Tang Xueqin Li Yi Cao Haiyang He Zhunyi Xie Jingbo Zhang Yongwen Chen Tingting Zhao Yuzhang Wu Xinyuan Zhou 

机构地区：[1]Institute of Immunology,College of Basic Medical Sciences,Third Military Medical University,Chongqing,400038,China [2]Institute for Cancer Medicine and School of Basic Medical 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

出　　处：《Cellular & Molecular Immunology》2021年第8期1969-1980,共12页中国免疫学杂志（英文版）

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.);the Chongqing Basic and Frontier Research Project(No.cstc2015jcyjBX0086 to H.He.).

摘　　要：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 LXRβdeficiency 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-7Rαexpression in wild-type mice but not in LXRβ-deficient mice.Mechanistically,LXRβpositively regulated the expression of IL-7Rαvia direct binding to the Il7r allele in SP thymocytes,and forced expression of IL-7Rαor Bcl2 restored the survival of LXRβ-defective SP thymocytes.Thus,our results indicate that LXRβfunctions as an important transcription factor upstream of IL-7Rαto promote the survival of SP thymocytes.

关 键 词：LXRβ IL-7Rα Single-positive thymocytes Cell survival Transcriptional regulation 

分 类 号：R392[医药卫生—免疫学]