Cell Competition, the Kinetics of Thymopoiesis, and Thymus Cellularity Are Regulated by Double-Negative 2 to 3 Early Thymocytes

• DOI: 10.1016/j.celrep.2020.107910
• Publication Date: 2020-07-21T14:38:43Z
• Authors: Camila V. Ramos; Luna Ballesteros-...; Joana G. Silva; Rafael A. Paiva; Marta F. Nogueira; Jorge Carneiro; Erida Gjini; Vera C. Martins
• Keywords: 0301 basic medicine; 0303 health sciences; Thymocytes; Interleukin-7; Cell Cycle; Cell Count; Cell Differentiation; Mice, Transgenic; Thymus Gland; DNA-Binding Proteins; Mice, Inbred C57BL; Kinetics; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Cell Competition; Animals; Cell Proliferation

SUMMARYCell competition in the thymus is a homeostatic process that drives turnover. If the process is impaired, thymopoiesis can be autonomously maintained for several weeks, but this causes leukemia. We aimed to understand the impact of cell competition on thymopoiesis, identify the cells involved and determine how the process is regulated. Using thymus transplantation experiments we found that cell competition occurs within the double negative 2 (DN2) and 3 early (DN3e) thymocytes and inhibits thymus autonomy. Furthermore, the expansion of DN2b is regulated by a negative feedback loop imposed by double positive thymocytes and determines the kinetics of thymopoiesis. This feedback loop impacts on cell cycle duration of DN2b, in a response controlled by interleukin 7 availability. Altogether, we show that thymocytes do not merely follow a pre-determined path if provided with the correct signals. Instead, thymopoiesis dynamically integrates cell autonomous and non-cell autonomous aspects that fine-tune normal thymus function.