Plasmacytoid dendritic cells in patients with autoimmune thyroid disease
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Background: Patients with autoimmune thyroid diseases (AITD)show defects in immunoregulatory mechanisms. Here in we assessed the expression of different regulatory receptors in circulating and thyroid dendritic cells (DCs). Design: Peripheral blood samples from 49 patients with Hashimoto%27s thyroiditis, 35 with Graves%27 disease, and 34 healthy subjects were studied. Clinical parameters included grades of goiter and ophthalmopathy, thyroid function, and antibody tests. Thyroid tissue samples from 10 AITD patients were also analyzed. Levels of DCs and their expression of different regulatory molecules (IDO, ILT2, ILT3, PSGL-1, PD-L1) were studied. In vitro interferon-α response by plasmacytoid DCs (pDCs) and tryptophan (Trp) metabolites were determined. Results: Significant low levels of pDCs, but not conventional DCs, were detected in the peripheral blood from AITD patients, mainly in those with severe disease. Furthermore, a diminished expression of ILT3, PSGL-1, and CD69 by peripheral blood pDCs from AITD patients was observed. An increased number of pDCs was found in thyroid tissue, showing a diminished expression of ILT3 and PSGL-1. A lower proportion of IDO pDCs, a significant increase in Trp levels, a decrease in the kyneruine/Trp ratio, and an increased in vitro interferon-α response were present in AITD patients. Finally, a significant correlation was found between the in vitro synthesis of IL-10 by stimulated T cells and expression of IDO by pDCs. Conclusions: The diminished number of pDCs in the peripheral blood from AITD patients as well as their abnormal phenotype could contribute significantly to the pathogenesis. Copyright © 2013 by The Endocrine Society.
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Background: Patients with autoimmune thyroid diseases (AITD)show defects in immunoregulatory mechanisms. Here in we assessed the expression of different regulatory receptors in circulating and thyroid dendritic cells (DCs). Design: Peripheral blood samples from 49 patients with Hashimoto's thyroiditis, 35 with Graves' disease, and 34 healthy subjects were studied. Clinical parameters included grades of goiter and ophthalmopathy, thyroid function, and antibody tests. Thyroid tissue samples from 10 AITD patients were also analyzed. Levels of DCs and their expression of different regulatory molecules (IDO, ILT2, ILT3, PSGL-1, PD-L1) were studied. In vitro interferon-α response by plasmacytoid DCs (pDCs) and tryptophan (Trp) metabolites were determined. Results: Significant low levels of pDCs, but not conventional DCs, were detected in the peripheral blood from AITD patients, mainly in those with severe disease. Furthermore, a diminished expression of ILT3, PSGL-1, and CD69 by peripheral blood pDCs from AITD patients was observed. An increased number of pDCs was found in thyroid tissue, showing a diminished expression of ILT3 and PSGL-1. A lower proportion of IDO%2b pDCs, a significant increase in Trp levels, a decrease in the kyneruine/Trp ratio, and an increased in vitro interferon-α response were present in AITD patients. Finally, a significant correlation was found between the in vitro synthesis of IL-10 by stimulated T cells and expression of IDO by pDCs. Conclusions: The diminished number of pDCs in the peripheral blood from AITD patients as well as their abnormal phenotype could contribute significantly to the pathogenesis. Copyright © 2013 by The Endocrine Society.
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alpha interferon; CD69 antigen; cell surface receptor; immunoglobulin like transcript 1; immunoglobulin like transcript 3; immunoglobulin like transcript 4; indoleamine 2,3 dioxygenase; kynurenine; P selectin glycoprotein ligand 1; programmed death 1 ligand 1; programmed death 1 ligand 2; thyroglobulin antibody; thyroid peroxidase antibody; thyrotropin receptor antibody; tryptophan; unclassified drug; adult; analytical parameters; antibody blood level; article; autoimmune thyroiditis; cell count; controlled study; cytokine production; disease severity; endocrine ophthalmopathy; female; goiter; Graves disease; Hashimoto disease; human; human cell; human tissue; immunoassay; immunological tolerance; immunopathogenesis; immunoregulation; in vitro study; kynurenine tryptophan ratio; lymphocytic infiltration; major clinical study; male; phenotype; plasmacytoid dendritic cell; priority journal; protein expression; quantitative analysis; T lymphocyte activation; thyroid function; Adult; Autoantibodies; Cells, Cultured; Cytokines; Dendritic Cells; Female; Goiter; Graves Disease; Hashimoto Disease; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interferon-alpha; Male; Middle Aged; Severity of Illness Index; Thyroid Function Tests; Thyroid Gland; Tryptophan
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