Abstract
Thymic epithelial cells (TECs) support T cell development in the thymus. Cortical thymic epithelial cells (cTECs) facilitate positive selection of developing thymocytes whereas medullary thymic epithelial cells (mTECs) facilitate the deletion of self-reactive thymocytes in order to prevent autoimmunity. The mTEC compartment is highly dynamic with continuous maturation and turnover, but the genetic regulation of these processes remains poorly understood. MicroRNAs (miRNAs) are important regulators of TEC genetic programs since miRNA-deficient TECs are severely defective. However, the individual miRNAs important for TEC maintenance and function and their mechanisms of action remain unknown. Here, we demonstrate that miR-205 is highly and preferentially expressed in mTECs during both thymic ontogeny and in the postnatal thymus. This distinct expression is suggestive of functional importance for TEC biology. Genetic ablation of miR-205 in TECs, however, neither revealed a role for miR-205 in TEC function during homeostatic conditions nor during recovery from thymic stress conditions. Thus, despite its distinct expression, miR-205 on its own is largely dispensable for mTEC biology.
Highlights
Thymic epithelial cells (TECs) are critical mediators of T cell development in the thymus
In order to identify miRNAs differentially expressed in medullary thymic epithelial cells, we purified thymic cell subsets from adult mice by flow cytometric cell sorting
To begin the tedious process of functionally characterizing individual miRNAs in TECs we chose to focus on miR-205 because of the following reasons: a) its high signal intensity in medullary thymic epithelial cells (mTECs), b) its differential expression in mTECs when compared to CD45+ cells and Cortical thymic epithelial cells (cTECs) (Fig 1A–1C), c) no other known miRNA shares the same seed sequence, d) miR-205-deficient mice are among the few miRNA-deficient mice that display neonatal lethality indicating that miR-205 has non-redundant functions at least in certain cells [36, 37]
Summary
Thymic epithelial cells (TECs) are critical mediators of T cell development in the thymus. MTECs eliminate self-reactive thymocytes from the developing T cell pool by displaying a repertoire of tissue-specific antigens (TSAs) whose expression is normally limited to peripheral tissues [3,4,5,6]. This ectopic expression of TSAs is largely dependent on autoimmune regulator (Aire), which is expressed in a mature subset of mTECs [7,8,9]. Patients and mice with defects in Aire develop multi-organ autoimmune disease, which emphasizes the importance of TSA expression in mTECs as a means to promote central T cell tolerance [7, 10,11,12]
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