The role of retinoic acid signaling in thymic function

Retinoic acid (RA) is a vitamin A metabolite and member of the large family of retinoids that have been used in treatment of various forms of cancer and skin disorders. Also, vitamin A deficiency is associated with impaired ability to fight infections and RA has been shown to shape peripheral immune responses. However, little is known about the role of RA in the development of immune cells. We are currently investigating the role of RA signaling in thymic function. In the thymus, thymic epithelial cells (TEC) are providing the specialized microenvironment that supports T cell development and proper TEC maturation and homeostasis is required for the generation of a functional T cell pool. TEC development and differenti-ation is dependent on crosstalk with immune and stromal cells in the thymus and previous work of our group has suggested RA as a potential key player in this process. To study the role of RA signaling in TEC homeostasis and function in vivo we are using a transgenic mouse model where RA signaling is blocked in the TEC compartment. Thereby we could show that RA controls TEC subset composition and maturation postnatally, preferably in the cortical TEC compartment. Block of RA signaling in TEC also affects T cell development and results in reduced numbers of single positive (SP) thymocytes and naive CD8+ T cells in the periphery.These findings provide first in vivo evidence for a role of RA signaling in the adult thymus regarding TEC function and T cell development.