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Transcription factor YY1 is essential for iNKT cell development.
Xijun Ou1,2, Jianxin Huo3, Yuhan Huang3
1Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, 138668, Singapore. ouxj@sustc.edu.cn.
Cellular & Molecular Immunology
|March 4, 2018
Summary
The transcription factor Yin Yang 1 (YY1) is crucial for invariant natural killer T (iNKT) cell development. YY1 regulates iNKT cell survival and PLZF expression, essential for their formation.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Invariant natural killer T (iNKT) cells are critical immune cells that develop from CD4+CD8+ double-positive (DP) thymocytes.
- Their development requires prolonged DP thymocyte survival and strong T-cell receptor (TCR) signaling for PLZF expression.
Purpose of the Study:
- To investigate the role of the transcription factor Yin Yang 1 (YY1) in iNKT cell development.
- To elucidate the mechanisms by which YY1 influences iNKT cell formation.
Main Methods:
- Analysis of thymocyte development in YY1-deficient mice.
- Assessment of Vα14-Jα18 gene rearrangement and cell survival.
- Chromatin immunoprecipitation and deep-sequencing to identify YY1 target genes.
Main Results:
- YY1 deficiency caused a developmental block at the earliest iNKT progenitor stage.
- YY1-deficient thymocytes showed impaired survival but normal Vα14-Jα18 rearrangement.
- YY1 directly binds and activates the promoter of the PLZF gene, and BIM deletion did not rescue iNKT development.
Conclusions:
- YY1 is essential for iNKT cell development.
- YY1 regulates iNKT cell formation by controlling both cell survival and PLZF expression.
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