MicroRNA-205 regulates thymopoiesis under steady state and stress conditions (HEM7P.222)

Abstract

Abstract The thymus comprises an interconnected meshwork of epithelial cells (TECs) and thymocytes. This organ is exceedingly sensitive to stress, undergoing rapid involution in response to infection, trauma, radiation exposure, and/or glucocorticoid treatments. The nature of the stress predicates whether the epithelial cells, developing thymocytes, and/or both are affected. MicroRNAs are small noncoding RNAs that regulate cellular responses to stress and during regeneration. We discovered that miR-205 is a stress responsive, epithelial-specific miR that modulates thymopoiesis. Mice lacking miR-205 selectively in TECs exhibited a significant decline in thymopoiesis beginning at 8 weeks of age. When stressed with a dsRNA mimic (polyI:C), these mice exhibited a much more severe thymic atrophy compared to littermate controls. Quantification of the TEC subsets revealed a defect in the proliferative recovery of the cortical TECs lacking miR-205. This contributed to a significant reduction in the number of single positive CD4 and CD8 T cells, indicating that the capacity of the TECs to support selection processes at the CD4+CD8+ stage of thymopoiesis is compromised. Current experiments to determine how miR-205 regulates TEC function and proliferation are ongoing. The findings reveal an important role for miR-205 in thymopoiesis, which may be of therapeutic importance.