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Up-regulated β<inf>1</inf>-integrin expression in autoimmune thyroid disorders

Abstract:

Lymphocytic infiltration of the thyroid gland in autoimmune thyroid disorders requires, as a first step, their attachment to endothelial cells (EC) and, subsequently, interaction with thyrocytes and extracellular matrix proteins. Recent studies have focused on the pathophysiologic role of β1- integrins as adhesion receptors for extracellular matrix proteins and as cell-to-cell adhesion receptors. In this study, we examine by flow cytometry and immunohistochemical techniques the differences in expression of β1- integrins in thyrocytes and EC between normal thyroids and thyroid glands from patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). Remarkably, we found an up regulated de novo expression of very late antigen (VLA)-α6 subunit in thyrocytes in close proximity to lymphocyte infiltrates in GD and HT thyroid glands, with no reactivity in control thyroids. Moreover, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-β produced a significant enhancement of VLA-α6 expression in vitro in thyrocytes in culture. In addition, an up-regulated expression of VLA-α5 and β1 subunits was found in thyrocytes from GD and HT glands, specifically in those areas more severely inflamed. VLA-α2 was basally expressed in middle size and large vessels in control glands, with an increased expression in vessels of all sizes in HT and GD glands. Dendritic cells in thyroid lymphoid follicles were also positive for VLA-β1, α2 and α6 subunits. These results indicate the existence of an up-regulatory process in the expression of β1-integrins, particularly the α6 subunit, in several cell types from inflamed GD and HT thyroid glands, suggesting that these integrins could play a relevant role in localizing and perpetuating the autoimmune response in the thyroid gland in autoimmune thyroid disorders.