Global Transcriptional Profiling Reveals Distinct Functions of Thymic Stromal Subsets and Age-Related Changes during Thymic Involution

Abstract

Summary: Age-associated thymic involution results in diminished T cell output and function in aged individuals. However, molecular mediators contributing to the decline in thymic function during early thymic involution remain largely unknown. Here, we present transcriptional profiling of purified thymic stromal subsets from mice 1, 3, and 6 months of age spanning early thymic involution. The data implicate unanticipated biological functions for a subset of thymic epithelial cells. The predominant transcriptional signature of early thymic involution is decreased expression of cell-cycle-associated genes and E2F3 transcriptional targets in thymic epithelial subsets. Also, expression of proinflammatory genes increases with age in thymic dendritic cells. Many genes previously implicated in late involution are already deregulated by 3–6 months of age. We provide these thymic stromal data sets, along with thymocyte data sets, in a readily searchable web-based platform, as a resource for investigations into thymocyte:stromal interactions and mechanisms of thymic involution. : Heterogeneous thymic stromal cells regulate proper T cell development. Age-associated thymic involution results in diminished T cell output and immunity. Ki et al. now present transcriptional profiling of six thymic stromal subsets during early thymic involution. They conclude that diminished E2F3 activity in thymic epithelial cells and an augmented inflammatory signature in dendritic cells are early hallmarks of involution. Data are provided on a web-based platform to facilitate discovery of molecular mediators of thymocyte:stromal cell crosstalk and early thymic involution.