Does androgen signaling cause thymic involution? (111.34)

Abstract

Abstract The thymus is the main source of naïve T cell output. As the body ages, the thymus undergoes involution, causing a drop in naïve T cell availability in the peripheral T cell pool. The molecular mechanisms underpinning thymic involution are not well characterized. However, androgen signaling has been associated with involution based on increases in thymus size and thymocyte number in both sex steroid ablated (SSA) mice and those lacking functional androgen receptor (Ar). However, to date there is no clear cellular target or mechanism by which androgen signaling affects involution. The available data consistently point to a thymic stromal target as the major site of androgen action in the thymus. Among these stromal cell types, thymic epithelial cells (TECs) express Ar and have been shown to increase proliferation and production of specific effectors such as CCL25 in response to castration. We have used a Cre-LoxP strategy to selectively delete Ar in TECs. Evaluations of these mice present compelling evidence that TECs are directly involved in androgen signaling within the thymus. While TEC-selective Ar deletion does cause increased thymus size and thymocyte numbers, these mice differ in several ways from previous reports on global Ar deletion or SSA, leading to the possibility that current models of the role of androgens in postnatal thymus may need to be re-evaluated.