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The thymus is a primary lymphoid organ that is important for T cell development. In the thymus, developing T cells are deleted if they express receptors that could cause dangerous immune attacks against the body’s own proteins. This process is known as central tolerance.
CD4 and CD8 T cells develop in the thymus with their transcription programs controlled by ThPOK and Runx3, respectively. Here the authors show that a pre-commitment event modulated by the transcription factor, Bcl11b, is required for the proper expression of ThPOK and Runx3 and correct CD4/CD8 lineage commitment.
The generation of a diverse T cell repertoire depends on heterogeneous populations of thymic epithelial cells (TECs). Here, the authors explain how different subsets of TECs support and coordinate different stages of T cell development to ensure the selection of a functional and self-tolerant T cell repertoire.
Sirtuin-1 (Sirt1), a protein deacetylase known for its multiple cellular functions, including roles in metabolism, stress response and aging, is a post-translational modulator of autoimmune regulator (Aire) in central immunotolerance.