Triiodothyronine modulates thymocyte migration

Triiodothyronine (T(3)) exerts several effects on thymus physiology. In this sense, T(3) is known to stimulate thymic microenvironmental cells to enhance the production of extracellular matrix (ECM) moieties, which are relevant in thymocyte migration. Here, we further investigated the in vivo influence of T(3) on ECM production, as well as on ECM-related T-cell migration events. For this, BALB/c mice were subjected to two protocols of T(3) treatment: long-term (30 days) i.p. daily T(3) injections or short-term (16 h) after a single T(3) intrathymic injection. These two treatments did promote an enhancement in the expression of fibronectin and laminin, in both cortex and medullary regions of the thymic lobules. As revealed by the long-term treatment, the expression of ECM protein receptors, including VLA-4, VLA-5 and VLA-6, was also increased in thymocyte subsets issued from T(3)-treated mice. We further used thymic nurse cells (TNC) as an in vitro system to study the ECM-related migration of immature thymocytes in the context of thymic epithelial cells. Even a single intrathymic injection of T(3) resulted in an increase in the ex vivo exit of thymocytes from TNC lymphoepithelial complexes. Accordingly, when we evaluated thymocyte migration in transwell chambers pre-coated with ECM proteins, we found an increase in the numbers of migrating cells, when thymocytes were derived from T(3)-treated mice. Overall, our data show that in vivo intrathymic short-term i.p. long-term T(3) treatments are able to modulate thymocyte migration, probably via ECM-mediated interactions.