NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection

Jianrong Wang, Nanhai He, Na Zhang, Dexian Quan, Shuo Zhang, Caroline Zhang, Ruth T. Yu, Annette R. Atkins, Ruihong Zhu, Chunhui Yang, Ying Cui, Christopher Liddle, Michael Downes, Hui Xiao, Ye Zheng, Johan Auwerx, Ronald M. Evans () and Qibin Leng ()
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Jianrong Wang: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Nanhai He: Salk Institute for Biological Studies
Na Zhang: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Dexian Quan: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Shuo Zhang: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Caroline Zhang: Salk Institute for Biological Studies
Ruth T. Yu: Salk Institute for Biological Studies
Annette R. Atkins: Salk Institute for Biological Studies
Ruihong Zhu: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Chunhui Yang: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Ying Cui: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Christopher Liddle: University of Sydney
Michael Downes: Salk Institute for Biological Studies
Hui Xiao: Chinese Academy of Sciences; University of Chinese Academy of Sciences
Ye Zheng: The Salk Institute for Biological Studies
Johan Auwerx: École Polytechnique Fédérale de Lausanne
Ronald M. Evans: Salk Institute for Biological Studies
Qibin Leng: Chinese Academy of Sciences; University of Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Thymocytes must pass both positive and negative selections to become mature T cells. Negative selection purges thymocytes whose T-cell receptors (TCR) exhibit high affinity to self-peptide MHC complexes (self pMHC) to avoid autoimmune diseases, while positive selection ensures the survival and maturation of thymocytes whose TCRs display intermediate affinity to self pMHCs for effective immunity, but whether transcriptional regulation helps conserve positively selected thymocytes from being purged by negative selection remains unclear. Here we show that the specific deletion of nuclear receptor co-repressor 1 (NCoR1) in T cells causes excessive negative selection to reduce mature thymocyte numbers. Mechanistically, NCoR1 protects positively selected thymocytes from negative selection by suppressing Bim expression. Our study demonstrates a critical function of NCoR1 in coordinated positive and negative selections in the thymus.

Date: 2017
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DOI: 10.1038/s41467-017-00931-8

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