ABSTRACT
PURPOSE: To study the levels of pathogenic and non-pathogenic Th17 and Th22 cells in autoimmune thyroid disorders patients. Although Th17 cells seem to play an important role in the pathogenesis of thyroid autoimmune disorders, the specific subsets of these lymphocytes have not been analyzed in this condition. METHODS: We assessed the levels of Th17 (pathogenic and non-pathogenic) and Th22 cells in peripheral blood and thyroid glands of autoimmune thyroid disorders patients (n = 26, 16 with Graves' disease and 10 with Hashimoto's thyroiditis) and 15 healthy controls by multi-parametric flow cytometry and immunofluorescence microscopy. RESULTS: We found increased levels of pathogenic Th17 lymphocytes and Th22 cells in peripheral blood from autoimmune thyroid disorders patients. In addition, these cells were detected in thyroid glands from HT patients. Furthermore, we found significant correlations between the levels of these cells and disease activity, disease duration, and the presence of ophthalmopathy. CONCLUSIONS: The increased levels of pathogenic Th17 lymphocytes and Th22 cells in autoimmune thyroid disorders suggest their involvement in the pathogenesis of this condition.
Subject(s)
Autoimmunity , Graves Disease/immunology , Hashimoto Disease/immunology , Lymphocytosis/etiology , T-Lymphocytes, Helper-Inducer/immunology , Th17 Cells/immunology , Thyroid Gland/immunology , Adult , Autoantibodies/analysis , Cells, Cultured , Female , Flow Cytometry , Graves Disease/metabolism , Graves Disease/pathology , Graves Disease/physiopathology , Graves Ophthalmopathy/etiology , Hashimoto Disease/metabolism , Hashimoto Disease/pathology , Hashimoto Disease/physiopathology , Humans , Iodine/urine , Lymphocyte Activation , Lymphocyte Count , Male , Microscopy, Fluorescence , Middle Aged , Severity of Illness Index , T-Lymphocytes, Helper-Inducer/metabolism , T-Lymphocytes, Helper-Inducer/pathology , Th17 Cells/metabolism , Th17 Cells/pathology , Thyroid Gland/metabolism , Thyroid Gland/pathology , Thyroid Gland/physiopathology , Thyroid Hormones/bloodABSTRACT
Different immune cell subsets have a relevant role in the pathogenesis of and tissue damage seen in autoimmune thyroid diseases (AITD), including T regulatory (Treg) lymphocytes and T helper (Th) 17 cells. There are several types of CD4+ Treg cells (Foxp3+, CD69+, Tr1), which are able to prevent the appearance of autoimmune diseases, down regulating the immune response and the inflammatory phenomenon. However, despite their presence in peripheral blood and thyroid tissue from patients with AITD, these cells are apparently unable to put down the autoimmune process. Moreover, many reports indicate the involvement of Th17 cells in chronic inflammatory diseases, including AITD. Nevertheless, it is now evident that these lymphocytes show a remarkable plasticity, giving rise to anti-inflammatory (including Treg lymphocytes) and pro-inflammatory cell subtypes. Nowadays, both Treg and Th17 cells must be considered as key elements in the pathogenesis of AITD as well as plausible potential targets for the next generation of therapeutic options of this condition.
Subject(s)
T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Thyroiditis, Autoimmune/immunology , Animals , Humans , T-Lymphocytes, Regulatory/pathology , Th17 Cells/pathology , Thyroid Gland/immunology , Thyroiditis, Autoimmune/pathologyABSTRACT
OBJECTIVE: Autoimmune thyroid disease (AITD) is characterized by different defects in immunoregulatory mechanisms. The immunoglobulin-like transcript receptor 2 (ILT2) or leukocyte Ig-like receptor 1 (LIRB1/CD85j) exerts an important immunoregulatory role. We hypothesized that the lymphocytes from AITD patients have a diminished expression and function of ILT2. The aim of this study was to investigate the expression and function of ILT2 in lymphocytes from patients with AITD. DESIGN AND METHODS: In this study, 18 patients with Hashimoto's thyroiditis (HT), 20 with Graves' disease, and 26 healthy controls were studied. ILT2 expression was analyzed by flow cytometry and immunohistochemistry in peripheral blood mononuclear cells (PBMC) and thyroid tissue. The regulatory function of ILT2 was assessed by an assay of inhibition of lymphocyte proliferation and by an analysis of cell cycle progression. The effect of ILT2 on cytokine synthesis was also evaluated. RESULTS: We found a significant increased expression of ILT2 by lymphocytes in AITD patients. ILT2 was also detected in the leukocyte infiltrate of thyroid tissue from HT patients. On the contrary, a significant diminished inhibitory activity of ILT2 on cell proliferation was observed in AITD patients. In addition, PBMC from AITD patients showed a diminished synthesis of interleukin 10 on ILT2 engagement. CONCLUSIONS: The abnormal expression and function of ILT2 detected in AITD suggests that this receptor may participate in the pathogenesis of this condition.