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Transcription factor YY1 is essential for iNKT cell development

Cellular & Molecular Immunology (2018) | Download Citation

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Abstract

Invariant natural killer T (iNKT) cells develop from CD4+CD8+ double-positive (DP) thymocytes and express an invariant Vα14–Jα18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα14–Jα18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage. YY1-deficient thymocytes underwent normal Vα14–Jα18 gene rearrangements, but exhibited impaired cell survival. Deletion of the apoptotic protein BIM failed to rescue the defect in iNKT cell generation. Chromatin immunoprecipitation and deep-sequencing experiments demonstrated that YY1 directly binds and activates the promoter of the Plzf gene. Thus, YY1 plays essential roles in iNKT cell development by coordinately regulating cell survival and PLZF expression.

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Acknowledgements

We thank Ms Lim Wei Lee for sample processing and plasmid construction. We also thank other members of the laboratory for insightful discussion and the A*STAR Biomedical Research Council for grant support.

Author information

Affiliations

  1. Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, 138668, Singapore

    • Xijun Ou
    • , Jianxin Huo
    • , Yuhan Huang
    • , Yan-Feng Li
    • , Shengli Xu
    •  & Kong-Peng Lam
  2. Department of Biology, Southern University of Science and Technology, Shenzhen, 518055, China

    • Xijun Ou
  3. Department of Physiology, National University of Singapore, Singapore, 117599, Singapore

    • Shengli Xu
    •  & Kong-Peng Lam
  4. Department of Microbiology and Immunology, National University of Singapore, Singapore, 117599, Singapore

    • Kong-Peng Lam
  5. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore

    • Kong-Peng Lam
  6. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore

    • Kong-Peng Lam

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Contributions

X.O., S.X., and K.-P.L. designed the experiments and wrote the paper. X.O., J.H., Y.H., and Y.-F.L. conducted the experiments.

Competing interests

The authors declare no competing interests.

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Correspondence to Xijun Ou or Shengli Xu or Kong-Peng Lam.

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https://doi.org/10.1038/s41423-018-0002-6