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NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive
Jianrong Wang1, Nanhai He2, Na Zhang1,3
1CAS Key Laboratory of Molecular Virology & Immunology, Unit of Immune Regulation, Institut Pasteur of Shanghai, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, 200031, China.
Nature Communications
|October 18, 2017
Summary
Nuclear receptor co-repressor 1 (NCoR1) prevents autoimmune diseases by regulating T cell selection. Deleting NCoR1 in T cells leads to excessive negative selection, reducing mature T cell numbers.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- T cell maturation involves positive and negative selection processes.
- Negative selection eliminates high-affinity T cell receptors (TCRs) to prevent autoimmunity.
- Positive selection promotes survival of thymocytes with intermediate TCR affinity for effective immunity.
Purpose of the Study:
- To investigate the role of transcriptional regulation in preventing positively selected thymocytes from undergoing negative selection.
- To elucidate the function of nuclear receptor co-repressor 1 (NCoR1) in T cell selection.
Main Methods:
- Specific deletion of NCoR1 in T cells.
- Analysis of thymocyte populations and mature T cell numbers.
- Investigation of Bim expression levels.
Main Results:
- Specific deletion of NCoR1 in T cells resulted in excessive negative selection.
- Reduced numbers of mature thymocytes were observed upon NCoR1 deletion.
- NCoR1 was found to suppress Bim expression, thereby protecting positively selected thymocytes from negative selection.
Conclusions:
- NCoR1 plays a critical role in the coordinated regulation of positive and negative selection in the thymus.
- NCoR1 functions to inhibit negative selection and promote thymocyte survival by suppressing Bim expression.