Up-regulated beta1-integrin expression in autoimmune thyroid disorders.
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 beta1-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 beta1-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)-alpha6 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-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-1beta produced a significant enhancement of VLA-alpha6 expression in vitro in thyrocytes in culture. In addition, an up-regulated expression of VLA-alpha5 and beta1 subunits was found in thyrocytes from GD and HT glands, specifically in those areas more severely inflamed. VLA-alpha2 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-beta1, alpha2 and alpha6 subunits. These results indicate the existence of an up-regulatory process in the expression of beta1-integrins, particularly the alpha6 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.
Marazuela
M
M
Department of Endocrinology, Hospital de la Princesa, Universidad Autónoma, Madrid, Spain.
De Landázuri
M O
MO
Larrañaga
E
E
Sánchez-Madrid
F
F
D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013959:Thyroid Diseases / Q000276:immunology*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation
D001324:Autoantigens; D019012:Integrin beta1; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma