Thymus articles from across Nature Portfolio

Regulation of thymocyte development by RNA-binding proteins is not fully characterized. Here the authors show the RBP ARPP21 interacting with the Rag1 3’-UTR to promote Rag1 expression, TCR rearrangement and an increased diversity of the TCR repertoire and that ARPP21 is down regulated by TCR stimulation.

Wang and colleagues revealed how oleic acid produced by thymic epithelial cells could affect the developing thymocytes to differentiate into peripheral regulatory T cells.

The molecular mechanisms that maintain thymic epithelial cell (TEC) identity throughout life are incompletely understood. Here, the authors demonstrate that the transcription factor, Ovol2, maintains post-natal TECs by preventing their epithelial-to-mesenchymal transition.

Although thymic function declines with age, the thymus also has the ability to regenerate following injury. Here, the authors demonstrate that IL-33 and type-2 innate lymphoid cells trigger the expansion of eosinophils following radiation injury, which in turn produce IL-4 to stimulate the recovery of the thymus mesenchyme during thymus regeneration.

Streets, Yosef, Robey and colleagues use multiomics analysis to generate a comprehensive timeline of the CD4⁺ and CD8⁺ T cell lineage commitment and identify sequential waves of TCR signaling that first initiate CD4⁺ T cell lineage differentiation and then CD8⁺ T cells lineage specification.

This Review summarizes how the processes of thymic selection together ensure that the T cell repertoire is fully functional and safe. In the thymus, T cell receptor signal strength is integrated with distinct stromal cues to result in positive or negative selection of thymocytes or the generation of regulatory cells.

Medullary thymic epithelial cells co-opt lineage-defining transcription factors to mimic numerous peripheral cell types and express their antigens against which maturing T cells can be tolerized.

FlipFlop mice, in which the coreceptor proteins encoded by the Cd4 and Cd8 loci are reversed, shed light on the importance of T cell receptor signal length versus signal strength in determining helper versus cytotoxic T cell lineage fates.

The Global Thymus Network convened virtually for ThymUS 2020 on 3–4 November 2020. Participants shared recent advances in thymus biology and enjoyed a reprieve from 2020 stressors.