Triiodothyronine Modulates Extracellular Matrix-Mediated Interactions between Thymocytes and Thymic Microenvironmental Cells

Abstract

Objectives: Thyroid hormones exert immunomodulatory activities and the thymus is one of their target organs. We previously showed that triiodothyronine (T₃) modulates thymic hormone production and extracellular matrix (ECM) expression by mouse thymic epithelial cells (TEC). This concept is enlarged herein by studying the effects of T₃ in human TEC preparations including primary cultures derived from thymic nurse cell complexes, as well as human and murine TEC lines. Methods and Results: We observed that in all cases, ECM ligands and receptors (such as fibronectin, laminin, VLA-5 and VLA-6) are enhanced in vitro, as ascertained by immunocytochemistry, ELISA and cytofluorometry. Moreover, thymocyte adhesion to these TEC preparations is augmented by T₃. Interestingly, TEC-thymocyte adhesion is also upregulated when thymocytes from T₃-treated mice adhere to untreated TEC cultures. Such an enhancing effect of T₃ upon TEC-thymocyte interactions is likely due to the increase in the expression of ECM ligands and receptors, since it is prevented when T₃-treated TEC cultures are incubated with anti-ECM antibodies prior to the adhesion assay. We then tested whether T₃ could modulate interactions between thymocytes and nonepithelial microenvironmental cells, exemplified herein by the phagocytic cells of the mouse thymic reticulum. In fact, in vitro treatment of these cells with T₃ increases ECM ligands and receptors and augments their ability to adhere to thymocytes. Lastly, using immunochemistry-based assays, we showed the presence of the nuclear T₃ receptor in all thymic microenvironmental cell preparations. Conclusion: Our data show that T₃ upregulates ECM-mediated heterocellular interactions of thymocytes with distinct thymic microenvironmental cells, in both humans and mice.

Triiodothyronine Modulates Thymocyte Migration

“…This should be placed in the context of a physiological role of ECM components in thymocyte migration-related events, such as adhesion of these cells to the thymic microenvironment [see reviews 22,23]. In this respect, we showed that TEC can produce ECM proteins, such as laminin, and that thymocyte adhesion to TEC can be abrogated by using anti-laminin or anti-laminin receptor antibodies [26,34,43,53,54]. Based on these observations, together with the findings showing that T 3 stimulated in vitro thymocyte/TEC adhesion [23] and the expression of ECM ligands and receptors by thymic cells, it was logical to predict that thyroid hormones could influence intrathymic T-cell migration.…”

Undetectable serum IgA and low IgM concentration in children with congenital hypothyroidism

“…In humans, thyroid hormones exert immunomodulatory activities and the thymus is one of their target organs [20]. Thyroid hormone receptors are Table 2 IgA and IgM serum concentrations in hypothyroidism patients and control groups…”

Cathepsin-L Influences the Expression of Extracellular Matrix in Lymphoid Organs and Plays a Role in the Regulation of Thymic Output and of Peripheral T Cell Number

“…The possibility exists that in nkt/nkt mice, the lack of CTSL leads to increases in other proteases-as it has been recently shown for procathepsin D in the thyroid gland of CTSL Ϫ/Ϫ mice (25)-which could be responsible for ECM degradation. In contrast, different factors have been involved in the control of ECM production (45)(46)(47). In human thymic epithelial cells, insulin growth factor-1 (IGF-1) stimulates the expression of laminin and fibronectin, as well as their receptors VLA-5 and VLA-6 (46).…”