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Tie-2 Is Overexpressed by Monocytes in Autoimmune Thyroid Disorders and Participates in Their Recruitment to the Thyroid Gland

Department of Immunology (N.F.-V., R.G.-A.), School of Medicine, Universidad Autónoma de San Luis Potosí, 78230 San Luis Potosí, México; Services of Endocrinology (N.F.-V., M.M.), Immunology (M.A.-P., C.C.-M., F.S.-M.) and Digestive Diseases (R.M.O.), and Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (R.M.-O.), Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain

Address all correspondence and requests for reprints to: Mónica Marazuela, M.D., Ph.D., Service of Endocrinology, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006 Madrid, Spain. E-mail: mmarazuela.hlpr{at}salud.madrid.org.

Context: The angiopoietin/Tie system seems to have an important role in the pathogenesis of inflammatory diseases. Although Tie-2 is mainly expressed by endothelium, it is also detected in monocytes, which participate in the development of angiogenic and inflammatory phenomena.

Aim: The aim was to study the expression and function of Tie-2 and their ligands, angiopoietin-1 (Ang-1) and Ang-2, in thyroid glands and monocytes from patients with autoimmune thyroid disease (AITD).

Design: We studied the expression of Tie-2, Ang-1, and Ang-2 by immunohistochemical techniques in surgical thyroid tissues from 17 patients with Graves’ disease, 8 with Hashimoto’s thyroiditis, and 3 healthy glands. In addition, we explored the expression and function of Tie-2 in peripheral blood monocytes from 17 patients with Graves’ disease, 11 with Hashimoto’s thyroiditis, and 14 healthy controls.

Results: We found that the expression of Ang-1, Ang-2, and Tie-2 was up-regulated in thyroid glands from AITD patients. Flow cytometry, immunofluorescence, ELISA, and RT-PCR analyses confirmed the synthesis and release of Ang-1, Ang-2, and Tie-2 by thyroid follicular cells (TFC) from AITD patients. In addition, these patients showed increased levels of Tie-2⁺ monocytes in the peripheral blood, which exhibited an enhanced chemotactic response to Ang-2 or autologous TFC.

Conclusions: Our data suggest that the Ang/Tie-2 system, through the participation of blood vessels, inflammatory cells, and TFC, may have an important role in the recruitment of monocytes to the thyroid gland and the pathogenesis of the tissue damage seen in AITD.