UP-REGULATED BETA(1)-INTEGRIN EXPRESSION IN AUTOIMMUNE THYROID-DISORDERS

Lymphocytic infiltration of the thyroid gland in autoimmune thyroid di sorders requires, as a first step, their attachment to endothelial cel ls (EC) and, subsequently, interaction with thyrocytes and extracellul ar matrix proteins. Recent studies have focused on the pathophysiologi c role of beta(1)-integrins as adhesion receptors for extracellular ma trix proteins and as cell-to-cell adhesion receptors. In this study, w e examine by flow cytometry and immunohistochemical techniques the dif ferences in expression of beta(1)-integrins in thyrocytes and EC betwe en normal thyroids and thyroid glands from patients with Graves' disea se (GD) and Hashimoto's thyroiditis (HT). Remarkably, we found an up-r egulated de novo expression of very late antigen (VLA)-alpha 6 subunit in thyrocytes in close proximity to lymphocyte infiltrates in GD and HT thyroid glands, with no reactivity in control thyroids. Moreover, i nterferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta produced a significant enhancement of VLA-alpha 6 expres sion in vitro in thyrocytes in culture. In addition, an up-regulated e xpression of VLA-alpha 5 and beta 1 subunits was found in thyrocytes f rom GD and HT glands, specifically in those areas more severely inflam ed. VLA-alpha 2 was basally expressed in middle size and large vessels in control glands, with an increased expression in vessels of all siz es in HT and GD glands. Dendritic cells in thyroid lymphoid follicles were also positive for VLA-beta 1, alpha 2 and alpha 6 subunits. These results indicate the existence of an up-regulatory process in the exp ression of beta(1)-integrins, particularly the alpha 6 subunit, in sev eral cell types from inflamed GD and HT thyroid glands, suggesting tha t these integrins could play a relevant role in localizing and perpetu ating the autoimmune response in the thyroid gland in autoimmune thyro id disorders.