Thymosin Beta 15 Alters the Spatial Development of Thymic Epithelial Cells.

ABSTRACT

The thymus is the most sensitive organ under various pathophysiological conditions, such as aging, starvation, and infection. As a key stromal cell for T cell development, it is well-known that thymic epithelial cells (TECs) play an important role in the thymus response to the external environment. Thymosin beta 15 (Tß15) is a G-actin binding protein secreted by TECs, it plays an important role in maintaining the dynamic balance of actin, angiogenesis, axonal formation, and wound healing, but the relationship between Tß15 and TECs is not clear yet. Here, we show the impact of Tß15 on the TEC's spatial development, as well as the T-cell differentiation and thymic output. As a result, TEC is the main effector cell of Tß15 in the thymus. Tß15 OX inhibits the chemotaxis of TECs to the medulla and subsequently blocks the positive selection of thymocytes from CD3+TCRß+CD4+CD8+ double positive cells to CD3+TCRß+CD4+CD8- single-positive (CD4SP) cells. Tß15-knockdown accelerates the reticular differentiation of astral TECs and medullary TECs. Importantly, mice implanted with Tß15-knockdown iTECs show high thymic output but low peripheral T cell maturity and activity. In a word, our results explain the role of Tß15 on the differentiation and function of TECs and provide a new perspective for understanding the process of thymus development and degeneration.